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|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22542186%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22542186%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 22542186 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 22542186"/>
|
||
<input type="hidden" name="email-subject-hash" value="c92e0401dd3262f36291cf9cf19cda5633286eeaa574cfbe8bb73fd16a9dbe77"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="22542186">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S0896-6273(12)00233-4"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=22542186&db=pubmed&nlmid=8809320"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="22542186"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/22542186/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=22542186&db=pubmed&nlmid=8809320"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="22542186"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/22542186/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/22542186/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="22542186" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F22542186%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="vMZV2x1jENhUa2UASwNTZ3IfDx1V4Fg0MzJ0FnuFeo4o4t0qvPqVtbeTbBJ7XgOk"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
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Dynactin is required for transport initiation from the distal axon
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Dynactin is required for transport initiation from the distal axon
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Dynactin is a required cofactor for the minus-end-directed microtubule motor cytoplasmic dynein. Mutations within the highly conserved CAP-Gly domain of dynactin cause neurodegenerative disease. Here, we show that the CAP-Gly domain is necessary to enrich dynactin at the distal end of primary neurons. While the CAP-Gly domain is not required for sustained transport along the axon, we find that the distal accumulation facilitates the efficient initiation of retrograde vesicular transport from the neurite tip. Neurodegenerative disease mutations in the CAP-Gly domain prevent the distal enrichment of dynactin thereby inhibiting the initiation of retrograde transport. Thus, we propose a model in which distal dynactin is a key mediator in promoting the interaction among the microtubule, dynein motor, and cargo for the efficient initiation of transport. Mutations in the CAP-Gly domain disrupt the formation of the motor-cargo complex, highlighting the specific defects in axonal transport that may lead to neurodegeneration.
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<p> Figure 1. The highly conserved CAP-Gly domain… </p>
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<p> Figure 1. The highly conserved CAP-Gly domain of p150 <sup> Glued </sup> is not required for axonal… </p>
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Figure 1. The highly conserved CAP-Gly domain of p150<sup>Glued</sup> is not required for axonal transport of lysosomes
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<div class="figure-caption-contents">(A) Schematic of the p150<sup>Glued</sup> subunit of dynactin. The CAP-Gly domain (green) binds both MTs and MT plus-end binding proteins. The basic domain (yellow) also independently binds MTs. The HMN7B (red) and the Perry syndrome (cyan) point mutations are shown below. (A′) Crystal structure of the CAP-Gly domain of p150<sup>Glued</sup> modified from (Honnappa et al., 2006) (PDB ID 2HKQ). The GKNDG motif is in green and the disease-associated mutations are colored as in (A). The HMN7B mutation is buried at the core of the CAP-Gly domain and may disrupt protein folding, while the Perry syndrome mutations are surface-exposed and may predominantly interfere with protein-protein interactions. Also see Movie S1. (B) Purified vesicles (V) from mouse brain enriched for LAMP1 were probed for p150<sup>Glued</sup> using a polyclonal antibody that recognizes both the full-length and p135 isoforms. (C) Purified vesicles had an increased ratio of full-length p150<sup>Glued</sup> to p135 compared to the high speed supernatant (HSS) and high-speed pellet (HSP) fractions. Mean ± SEM, <i>n</i>=3 vesicle purifications, ***<i>P</i><0.001 compared to HSS, one-way ANOVA Bonferroni post test. (D) Kymographs of LAMP1-RFP motility in primary dorsal root ganglion (DRG) neurons imaged at 4 days <i>in vitro</i> (DIV) after transfection with two scrambled siRNAs or two siRNAs to p150<sup>Glued</sup>. siRNAs were also transfected with wild-type full-length p150<sup>Glued</sup> (WT) or ΔCAP-Gly p150<sup>Glued</sup> (ΔCAP) resistant to the siRNA. Kymographs drawn along neurite processes represent movement over time so motile organelles appear as diagonal lines while paused organelles appear as vertical lines. Images were acquired at 366 ms per frame for 2.2 minutes; scale bars for the x and y-axes represent 10 μm and 20 seconds, respectively. Kymographs show the first 300 frames, full movies shown in Movie S2. (E) Lysosomal motility was quantified from the kymographs. Depletion of p150<sup>Glued</sup> significantly disrupted anterograde and retrograde motility and caused a corresponding increase in non-motile events. Expression of either wild-type or ⊗CAP-Gly p150<sup>Glued</sup> rescued this disruption. >800 vesicles were counted per condition. Mean ± SEM, <i>n</i>=12–15 neurons per condition, ***<i>P</i><0.001 compared to scrambled siRNAs, one-way ANOVA Bonferroni post test. Also see Figure S1.</div>
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<p> Figure 2. The CAP-Gly domain is necessary for the distal enrichment of dynactin in neurons </p>
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|
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|
||
<strong class="figure-label">
|
||
Figure 2. The CAP-Gly domain is necessary for the distal enrichment of dynactin in neurons
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Distal ends of DRG neurons expressing GFP were stained at 2 DIV for endogenous p150<sup>Glued</sup> or endogenous dynein heavy chain (DHC) and GFP, as a marker of cytoplasmic volume. These images were individually contrast enhanced to display both axonal and tip staining. The raw p150 and DHC data were divided by the corresponding raw GFP signal to create the ratio-image (R<sup>p150</sup>/<sub>GFP</sub> or R<sup>DHC</sup>/<sub>GFP</sub>). These images show the distal accumulation relative to GFP. These ratio-images were contrast enhanced to the same level and a heat map was applied to show the relative intensities of the ratio. The warmer colors represent a higher ratio, while cooler colors represent a lower ratio. (B) Line-scan quantification of the distal accumulation. The normalized ratio of endogenous dynactin or dynein fluorescence intensity to GFP intensity was determined along the length of the neurite tip. Expression as a ratio to soluble GFP controls for changes in cytoplasmic volume. Dynactin accumulated significantly more than dynein over the distal 15 μm of the neurite. Mean ± SEM, <i>n</i>≥41 neurite tips from 5–7 neurons per condition, ***<i>P</i><0.001, two-way ANOVA Bonferroni post test. (C) Images of the distal neurites of DRG neurons expressing myc-tagged full-length wild-type or ΔCAP-Gly p150<sup>Glued</sup> and GFP from a bicistronic vector at 2 DIV. Neurites were stained for myc and GFP and images individually contrast enhanced to display both axonal and tip staining. The corresponding ratio-images (R<sup>p150</sup>/<sub>GFP</sub>) were made from the raw imaging data and a heat map was applied as described in (A). (D) Line-scan analysis from the end of the neurite. The normalized ratio of myc-tagged p150<sup>Glued</sup> fluorescence intensity to GFP intensity was determined along the length of the neurite tip. Wild-type p150<sup>Glued</sup> accumulated significantly more over the distal 10 μm compared to ΔCAP-Gly p150<sup>Glued</sup>. Mean ± SEM, <i>n</i>≥29 neurite tips from 5–6 neurons per condition, ***<i>P</i><0.001, two-way ANOVA Bonferroni post test. Scale bars: 5 μm. Also see Figure S2.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
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||
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|
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data-slide-index="2"
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data-label-slug="figure-3">
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||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/bb1107859ae6/nihms-370380-f0003.jpg"
|
||
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||
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||
role="button"
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data-image-width="600"
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||
data-image-height="595"
|
||
data-image-alt="Figure 3"
|
||
data-pmc-id="PMC3347924"
|
||
data-figure-id="F3">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-2"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/2a316c7d4506/nihms-370380-f0003.gif"
|
||
alt="Figure 3" />
|
||
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<div class="caption-wrap">
|
||
|
||
|
||
|
||
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||
|
||
<strong class="figure-label">
|
||
<p> Figure 3. Kinesin-1, but not kinesin-2, contributes… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
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||
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|
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|
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|
||
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||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 3. Kinesin-1, but not kinesin-2, contributes to the distal localization of dynactin </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Distal… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 3. Kinesin-1, but not kinesin-2, contributes to the distal localization of dynactin
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Distal ends of DRG neurons expressing GFP, GFP-tagged KHC-stalk or GFP-tagged KHC-tail were stained at 2 DIV for endogenous p150<sup>Glued</sup> and GFP. These images were individually contrast enhanced to display both axonal and tip staining. The raw p150 data was divided by the corresponding raw GFP signal to create the ratio-image (R<sup>p150</sup>/<sub>GFP</sub>). These images show the distal accumulation relative to GFP. These ratio-images were contrast enhanced to the same level and a heat map was applied to show the relative intensities of the ratio. The warmer colors represent a higher ratio, while cooler colors represent a lower ratio. (B) Line-scan quantification of the distal accumulation. The normalized ratio of endogenous dynactin fluorescence intensity to GFP intensity was determined along the length of the neurite tip. The KHC-tail, a dominant-negative kinesin-1 inhibitor, significantly disrupted the localization of dynactin over the distal 9 μm of the neurite as compared to vector expressing neurons. Mean ± SEM, <i>n</i>≥46 neurite tips from 7–8 neurons per condition, ***<i>P</i><0.001, two-way ANOVA Bonferroni post test. (C) Distal ends of DRG neurons expressing GFP or GFP-tagged Kif3A-HL, a dominant-negative kinesin-2 inhibitor, were stained at 2 DIV for endogenous p150<sup>Glued</sup> and GFP. These images were individually contrast enhanced to display both axonal and tip staining. The ratio-images (R<sup>p150</sup>/<sub>GFP</sub>) were calculated from the raw imaging data and a heat map was applied as described in (A). (D) Line-scan quantification of the distal accumulation as described in (B). Kif3A-HL expression had no effect on the distal accumulation of dynactin. Mean ± SEM, <i>n</i>≥46 neurite tips from 7 neurons per condition. Also see Figure S3.</div>
|
||
|
||
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||
|
||
|
||
</figcaption>
|
||
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||
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||
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|
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|
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itemscope itemtype="http://schema.org/ImageObject"
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data-slide-index="3"
|
||
data-label-slug="figure-4">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/6fc81cb02256/nihms-370380-f0004.jpg"
|
||
itemprop="contentUrl"
|
||
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|
||
role="button"
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||
data-image-width="553"
|
||
data-image-height="600"
|
||
data-image-alt="Figure 4"
|
||
data-pmc-id="PMC3347924"
|
||
data-figure-id="F4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/d8e62cb04110/nihms-370380-f0004.gif"
|
||
alt="Figure 4" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="553">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="600">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
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<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 4. EBs are necessary to maintain… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
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||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 4. EBs are necessary to maintain the highly stable pool of distal dynactin </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A)… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 4. EBs are necessary to maintain the highly stable pool of distal dynactin
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) FRAP time-series of the distal tip of DRG neurons at 2 DIV expressing either EGFP or EGFP-p150<sup>Glued</sup>. The yellow box demarcates the photobleached region. Each image in the time-series was contrast enhanced equally. Also see Movie S3. (B) Mean FRAP recovery curve ± SEM, <i>n</i>=10–11 neurites per condition. Photobleaching occurred at time=0. (C) The mobile fraction for each individual FRAP trace was determined by fitting the trace to a single exponential equation. The mean mobile fraction was determined for EGFP and EGFP-p150<sup>Glued</sup> expressing neurons ± SEM, <i>n</i>=10–11 traces per condition, ****<i>P</i><0.0001, Student's t-test. (D) Quantification of EB1 binding as percent bound relative to wild-type. WT and ΔCAP p150<sup>Glued</sup> fragments were synthesized <i>in vitro</i> and incubated with either EB1-conjugated or empty beads. Mean ± SEM, <i>n</i>=4 independent experiments, *<i>P</i><0.05, Student's t-test. Also see Figure S5. (E) The number of EB3 comets was counted from time-lapse movies of DRG neurons at 2 DIV expressing mCherry-EB3. Distal neurite is defined as the distal 10 μm of the neurite while the midaxon is defined as a 10 μm region of the axon >50 μm proximal to the neurite end. Mean ± SEM, <i>n</i>=21 movies per condition, **<i>P</i><0.01, Student's t-test. (F) Lysate from DRG neurons at 4 DIV after treatment with either control siRNAs or siRNA directed against EB1 and EB3 was probed for EB1, EB3 and β-catenin. (G) Quantification by western blot of EB1 and EB3 levels after siRNA knockdown showed approximately 80% and 100% knockdown of EB1 and EB3, respectively. Western blot values were normalized to β-catenin as a loading control. (H) Distal ends of DRG neurons at 4 DIV stained for endogenous p150<sup>Glued</sup> and GFP after transfection with GFP and either control siRNAs or siRNAs against EB1 and EB3. These images were individually contrast enhanced to display both axonal and tip staining. The ratio-images (R<sup>p150</sup>/<sub>GFP</sub>) were calculated from the raw imaging data by dividing the raw p150 data by the corresponding raw GFP signal. These images show the distal accumulation relative to GFP. These ratio-images were contrast enhanced to the same level and a heat map was applied to show the relative intensities of the ratio. The warmer colors represent a higher ratio, while cooler colors represent a lower ratio. (I) Line-scan quantification of the distal accumulation. The normalized ratio of endogenous dynactin fluorescence intensity to GFP intensity was determined along the length of the neurite tip. Expression as a ratio to soluble GFP controls for changes in cytoplasmic volume. Knockdown of EB1 and EB3 significantly reduced the distal accumulation of dynactin over 7.8 μm from the distal axon. Mean ± SEM, <i>n</i>≥49 neurite tips from 9–12 neurons per condition, ***<i>P</i><0.001, two-way ANOVA Bonferroni post test. Scale bars: 5 μm.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
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|
||
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|
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|
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|
||
data-label-slug="figure-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/168b16498ab8/nihms-370380-f0005.jpg"
|
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|
||
role="button"
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data-image-width="600"
|
||
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|
||
data-image-alt="Figure 5"
|
||
data-pmc-id="PMC3347924"
|
||
data-figure-id="F5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/b2f8ddad97fe/nihms-370380-f0005.gif"
|
||
alt="Figure 5" />
|
||
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|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="600">
|
||
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|
||
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<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 5. The CAP-Gly domain enhances the… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
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|
||
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|
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|
||
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||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 5. The CAP-Gly domain enhances the retrograde flux of cargo from the distal axon </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
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|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 5. The CAP-Gly domain enhances the retrograde flux of cargo from the distal axon
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">DRG neurons were imaged at 4 DIV after transfection with siRNA to deplete endogenous p150<sup>Glued</sup> and rescued with either wild-type or ΔCAP-Gly p150<sup>Glued</sup>. The retrograde flux of LAMP1-RFP cargo from the end of the neurite was measured following photobleaching of a zone 10 μm proximal to the neurite end. Entry of cargos from the distal tip into this bleach zone was assessed with time-lapse imaging. Images were acquired at 2 frames per second for 5 seconds pre-photobleaching and 120 seconds post-photobleaching. (A) Kymographs of the photobleached zone were made prior to and subsequent to photobleaching to assess the retrograde flux of cargo from the distal neurite. Scale bars for the x and y-axes represent 5 μm and 20 seconds, respectively. On the right, for illustrative purposes, the retrograde moving cargos were traced over in blue, the time of photobleaching is marked in red and the point where flux measurements were made is in orange. (B) Retrograde vesicle flux was determined by counting the number of retrograde vesicles that moved at least 3.5 μm into the photobleached zone from the distal neurite. Rescue with ΔCAP-Gly p150<sup>Glued</sup> significantly decreased the flux from the distal neurite as compared to either rescue with wild-type p150<sup>Glued</sup> or control neurons not treated with siRNA. Mean ± SEM, <i>n</i>>11 neurites from 6–14 neurons per condition, **<i>P</i><0.01, compared to wild-type, one-way ANOVA Bonferroni post test. (C) Model for the function of the CAP-Gly domain of p150<sup>Glued</sup> in neurons. The CAP-Gly domain is necessary to distally enrich p150<sup>Glued</sup> in neurite tips and facilitate the flux of cargo from the neurite end. Also see Figure S4.</div>
|
||
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|
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||
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|
||
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|
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/31f9cce4afff/nihms-370380-f0006.jpg"
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|
||
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|
||
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|
||
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|
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|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/9c524b8fb790/nihms-370380-f0006.gif"
|
||
alt="Figure 6" />
|
||
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|
||
|
||
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||
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|
||
<strong class="figure-label">
|
||
<p> Figure 6. Decreased association of HMN7B mutant… </p>
|
||
</strong>
|
||
|
||
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||
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||
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|
||
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|
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|
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|
||
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||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 6. Decreased association of HMN7B mutant dynactin with dynein </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Myc-tagged wild-type (WT), HMN7B… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
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||
|
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|
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|
||
|
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|
||
<strong class="figure-label">
|
||
Figure 6. Decreased association of HMN7B mutant dynactin with dynein
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Myc-tagged wild-type (WT), HMN7B (G59S), Perry syndrome (G71R & Q74P) and ΔCAP-Gly p150<sup>Glued</sup> were co-expressed with wild-type HA-tagged p150<sup>Glued</sup> in COS-7 cells, LSS: low-speed supernatant. (B) Immunoprecipitation (IP) was performed using an anti-myc antibody. Immunoprecipitates were probed for the myc and HA-tagged p150<sup>Glued</sup> constructs to assess dimerization. Immunoblot (IB) for dynamitin/p50, a subunit of the dynactin complex, and the dynein intermediate chain, DIC, was performed to assess incorporation into the dynein-dynactin complex. GAPDH was probed for as a negative control. Quantification of p150<sup>Glued</sup> dimerization (C), incorporation into dynactin (D) and association with dynein (E), relative to wild-type. Insets above the graphs illustrate the association tested. Mean ± SEM, <i>n</i>=3–4 independent experiments, **<i>P</i><0.01 compared to wild-type, one-way ANOVA Bonferroni post test. Also see Figures S5 and S6.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
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|
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|
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|
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|
||
<a class="figure-link"
|
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/526dc8b41d5a/nihms-370380-f0007.jpg"
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|
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|
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|
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|
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|
||
data-image-alt="Figure 7"
|
||
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|
||
data-figure-id="F7">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957e/3347924/c4a97284d02f/nihms-370380-f0007.gif"
|
||
alt="Figure 7" />
|
||
</a>
|
||
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||
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|
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|
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<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 7. The HMN7B mutation, but not… </p>
|
||
</strong>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
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|
||
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|
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|
||
|
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|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 7. The HMN7B mutation, but not the Perry syndrome mutations, disrupts axonal transport </p>
|
||
</strong>
|
||
|
||
|
||
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<strong class="figure-label">
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Figure 7. The HMN7B mutation, but not the Perry syndrome mutations, disrupts axonal transport
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<div class="figure-caption-contents">(A) Kymographs from live-cell time-lapse imaging of LAMP1-RFP in DRG neurons at 2 DIV expressing wild-type (WT), ΔCAP-Gly, CC1, HMN7B (G59S) or Perry syndrome (G71R & Q74P) p150<sup>Glued</sup>. Images were acquired at 366 ms per frame for 2.2 minutes; scale bars for the x and y-axes represent 10 μm and 20 seconds, respectively. Kymographs show the first 180 frames, full movies shown in Movies S4 and S5. (B) Quantification of vesicle motility from the kymographs showed that only the HMN7B (G59S) mutation and CC1 disrupt motility. >575 vesicles were counted per condition. Mean ± SEM, <i>n</i>=5–8 neurons per condition, *<i>P</i><0.05, **<i>P</i><0.01 compared to wild-type, one-way ANOVA Bonferroni post test. (C–E) Individual tracks from the kymographs were analyzed. (C) Mean anterograde and retrograde instantaneous velocities ± SD, <i>n</i>>800 instantaneous velocities per condition per direction. Also see Figure S7. Quantification of the number of pauses per track (D) and motility switches per track (E). Mean ± SEM, <i>n</i>>23 vesicles per condition, **<i>P</i><0.01 compared to wild-type, one-way ANOVA Bonferroni post test.</div>
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<p> Figure 8. Perry syndrome mutant disrupts flux… </p>
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<p> Figure 8. Perry syndrome mutant disrupts flux from the distal neurite </p>
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<div class="figure-caption-contents"><p> (A) DRG neurons were… </p></div>
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Figure 8. Perry syndrome mutant disrupts flux from the distal neurite
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</strong>
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<div class="figure-caption-contents">(A) DRG neurons were stained at 2 DIV for myc-tagged wild-type (WT), HMN7B (G59S) or Perry syndrome (G71R & Q74P) p150<sup>Glued</sup> and GFP, a marker of cytoplasmic volume, expressed from a bicistronic vector. These distal neurite images were individually contrast enhanced to display both axonal and tip staining. The raw myc-p150 data was divided by the corresponding raw GFP signal to create the ratio-image (R<sup>p150</sup>/<sub>GFP</sub>), which shows the distal accumulation relative to GFP. These ratio-images were contrast enhanced to the same level and a heat map was applied to show the relative intensities of the ratio. The warmer colors represent a higher ratio, while cooler colors represent a lower ratio. Scale bar: 5 μm. (B) Line-scan analysis from the neurite tip. The normalized ratio of myc-p150<sup>Glued</sup> to GFP fluorescence intensity was determined along the length of the neurite. Wild-type p150<sup>Glued</sup> accumulated significantly more over the first 14 μm as compared to mutant p150<sup>Glued</sup>. The WT-p150 data was replotted from Figure 2D. Mean ± SEM, <i>n</i>≥29 neurite tips from 4–6 neurons per condition, ***<i>P</i><0.001 compared to wild-type, two-way ANOVA Bonferroni post test. (C) DRG neurons expressing wild-type or G71R p150<sup>Glued</sup> were imaged at 2 DIV. The retrograde flux of LAMP1-RFP from the neurite tip was measured following photobleaching of a zone 10 μm proximal to the end of the neurite. Entry of cargos from the distal tip into this bleach zone was assessed with time-lapse imaging. Images were acquired at 2 frames per second for 5 seconds pre-photobleaching and 120 seconds post-photobleaching. Kymographs of the photobleached zone were made prior to and subsequent to photobleaching to assess the retrograde flux of cargo from the distal neurite. (D) Retrograde vesicle flux was determined by counting the number of retrograde vesicles that moved at least 3.5 μm into the photobleached zone. The Perry syndrome (G71R) mutation dominantly decreased retrograde flux from the distal neurite. Mean ± SEM, <i>n</i>=14–16 neurites from 8 neurons per condition, **<i>P</i><0.01 Student's t-test. (E) Model of how the Perry syndrome and HMN7B mutations differentially disrupt dynactin function. The wild-type model is redrawn from Figure 5C. The Perry syndrome mutations decrease distal dynactin accumulation and reduce the flux of cargo from the neurite tip. The HMN7B mutation destabilizes dynactin, which decreases the association between dynein and dynactin and disrupts transport throughout the axon.</div>
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The CAP-Gly of p150: one domain, two diseases, and a function at the end.
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<span class="docsum-authors full-authors">Cronin MA, Schwarz TL.</span>
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<span class="docsum-journal-citation full-journal-citation">Neuron. 2012 Apr 26;74(2):211-3. doi: 10.1016/j.neuron.2012.04.003.</span>
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<span class="docsum-journal-citation short-journal-citation">Neuron. 2012.</span>
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Ahmed S, Sun S, Siglin AE, Polenova T, Williams JC. Disease-associated mutations in the p150(Glued) subunit destabilize the CAP-gly domain. Biochemistry. 2010;49:5083–5085.
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data-ga-action="add_to_search"
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data-ga-label=""Nuclear Proteins/metabolism"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Photobleaching"
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aria-controls="keyword-actions-mesh-terms-21"
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aria-expanded="false"
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data-pinger-ignore>
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Photobleaching
|
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</button><div id="keyword-actions-mesh-terms-21"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Photobleaching"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Photobleaching%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Photobleaching%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Photobleaching"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Protein Structure, Tertiary / genetics"
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Protein Structure, Tertiary / genetics
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</button><div id="keyword-actions-mesh-terms-22"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Protein Structure, Tertiary / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Protein+Structure%2C+Tertiary%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Protein+Structure%2C+Tertiary%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Protein Structure, Tertiary/genetics"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Protein Transport / genetics"
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Protein Transport / genetics
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</button><div id="keyword-actions-mesh-terms-23"
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aria-label="Dropdown menu for keyword Protein Transport / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Protein+Transport%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Protein Transport/genetics"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword RNA, Small Interfering / genetics"
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RNA, Small Interfering / genetics
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</button><div id="keyword-actions-mesh-terms-24"
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hidden
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aria-label="Dropdown menu for keyword RNA, Small Interfering / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22RNA%2C+Small+Interfering%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Small Interfering/genetics"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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RNA, Small Interfering / metabolism
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</button><div id="keyword-actions-mesh-terms-25"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword RNA, Small Interfering / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22RNA%2C+Small+Interfering%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22RNA%2C+Small+Interfering%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="RNA, Small Interfering/metabolism"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""RNA, Small Interfering/metabolism"[MeSH]"
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data-ga-category="search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Transfection"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-26"
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aria-expanded="false"
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data-pinger-ignore>
|
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Transfection
|
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</button><div id="keyword-actions-mesh-terms-26"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Transfection"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Transfection%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Transfection%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Transfection"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Transfection"
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data-ga-category="search_mesh"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Transfection"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Transfection"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Ubiquitin-Protein Ligases"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-27"
|
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aria-expanded="false"
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data-pinger-ignore>
|
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Ubiquitin-Protein Ligases
|
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</button><div id="keyword-actions-mesh-terms-27"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Ubiquitin-Protein Ligases"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Ubiquitin-Protein+Ligases%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Ubiquitin-Protein+Ligases%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Ubiquitin-Protein Ligases"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Ubiquitin-Protein+Ligases"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Ubiquitin-Protein Ligases"[MeSH]"
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data-ga-category="search"
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Add to Search
|
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</a></li></ul></div></div></div></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="substances" class="substances keywords-section">
|
||
<h2 class="title">
|
||
Substances
|
||
</h2>
|
||
|
||
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword DNA-Binding Proteins"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-0"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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DNA-Binding Proteins
|
||
</button><div id="keyword-actions-substances-0"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword DNA-Binding Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22DNA-Binding+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22DNA-Binding+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&keyword="DNA-Binding Proteins"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="DNA-Binding Proteins">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22DNA-Binding+Proteins%22"
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data-ga-category="search_mesh"
|
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data-ga-action="substance_link"
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data-ga-label="DNA-Binding Proteins">
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
|
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role="button"
|
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data-search-term=""DNA-Binding Proteins"[nm]"
|
||
data-ga-category="search"
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data-ga-action="add_to_search"
|
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data-ga-label=""DNA-Binding Proteins"[nm]"
|
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href="#">
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Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Dynactin Complex"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-1"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
||
Dynactin Complex
|
||
</button><div id="keyword-actions-substances-1"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Dynactin Complex"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Dynactin+Complex%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Dynactin+Complex%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Dynactin Complex"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Dynactin Complex">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Dynactin+Complex%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="Dynactin Complex">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Dynactin Complex"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Dynactin Complex"[nm]"
|
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Lamp1 protein, mouse"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-2"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Lamp1 protein, mouse
|
||
</button><div id="keyword-actions-substances-2"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Lamp1 protein, mouse"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Lamp1+protein%2C+mouse%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Lamp1+protein%2C+mouse%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Lamp1 protein, mouse"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Lamp1 protein, mouse">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Lamp1+protein%2C+mouse%22"
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data-ga-action="substance_link"
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Lamp1 protein, mouse"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Lysosomal Membrane Proteins"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-3"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
||
Lysosomal Membrane Proteins
|
||
</button><div id="keyword-actions-substances-3"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Lysosomal Membrane Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Lysosomal+Membrane+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Lysosomal+Membrane+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Lysosomal Membrane Proteins"[nm]"
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Search in PubMed
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|
||
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|
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Search in MeSH
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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|
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aria-expanded="false"
|
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|
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Microtubule-Associated Proteins
|
||
</button><div id="keyword-actions-substances-4"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Microtubule-Associated Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Microtubule-Associated+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Nuclear Proteins"
|
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tabindex="0"
|
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|
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aria-expanded="false"
|
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data-pinger-ignore>
|
||
Nuclear Proteins
|
||
</button><div id="keyword-actions-substances-5"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
||
aria-label="Dropdown menu for keyword Nuclear Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Nuclear+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Nuclear+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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data-search-term=""Nuclear Proteins"[nm]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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tabindex="0"
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|
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data-pinger-ignore>
|
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RNA, Small Interfering
|
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</button><div id="keyword-actions-substances-6"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword RNA, Small Interfering"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Trim27 protein, mouse"
|
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tabindex="0"
|
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|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
||
Trim27 protein, mouse
|
||
</button><div id="keyword-actions-substances-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Trim27 protein, mouse"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Trim27+protein%2C+mouse%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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|
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data-ga-action="substance_link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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role="button"
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data-search-term=""Trim27 protein, mouse"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Trim27 protein, mouse"[nm]"
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href="#">
|
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Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Ubiquitin-Protein Ligases"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-8"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
||
Ubiquitin-Protein Ligases
|
||
</button><div id="keyword-actions-substances-8"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Ubiquitin-Protein Ligases"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Ubiquitin-Protein+Ligases%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Ubiquitin-Protein+Ligases%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Ubiquitin-Protein Ligases"[nm]"
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data-ga-category="search"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Ubiquitin-Protein+Ligases%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Ubiquitin-Protein Ligases"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Glycine"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-9"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
||
Glycine
|
||
</button><div id="keyword-actions-substances-9"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Glycine"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Glycine%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Glycine%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Glycine"[nm]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Glycine%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="Glycine">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Glycine"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Glycine"[nm]"
|
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href="#">
|
||
Add to Search
|
||
</a></li></ul></div></div></div></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div id="related-links" class="related-links">
|
||
<h2 class="title">
|
||
Related information
|
||
</h2>
|
||
|
||
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=1">
|
||
Cited in Books
|
||
</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=2">
|
||
Gene
|
||
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=3">
|
||
MedGen
|
||
</a></li><li><a title="Related records in MedGen based on citations in GeneReviews and Medical Genetics Summaries" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_bookshelf_cited&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=4">
|
||
MedGen (Bookshelf cited)
|
||
</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=5">
|
||
Protein (RefSeq)
|
||
</a></li><li><a title="Related PubChem Compound" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=6">
|
||
PubChem Compound
|
||
</a></li><li><a title="Related PubChem Compound via MeSH" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound_mesh&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=7">
|
||
PubChem Compound (MeSH Keyword)
|
||
</a></li><li><a title="Related PubChem Substance" href="https://www.ncbi.nlm.nih.gov/pcsubstance?linkname=pubmed_pcsubstance&from_uid=22542186"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=22542186&ordinalpos=1&linkpos=8">
|
||
PubChem Substance
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="grants" class="grants">
|
||
<h2 class="title">
|
||
Grants and funding
|
||
</h2>
|
||
<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
|
||
title="All articles for grant 1F31NS073196/NS/NINDS NIH HHS/United States"
|
||
href="/?term=1F31NS073196%2FNS%2FNINDS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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1F31NS073196/NS/NINDS NIH HHS/United States
|
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</a></li><li class="grant-item"><a
|
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title="All articles for grant T32 AG000255/AG/NIA NIH HHS/United States"
|
||
href="/?term=T32+AG000255%2FAG%2FNIA+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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T32 AG000255/AG/NIA NIH HHS/United States
|
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</a></li><li class="grant-item"><a
|
||
title="All articles for grant 5T32AG000255/AG/NIA NIH HHS/United States"
|
||
href="/?term=5T32AG000255%2FAG%2FNIA+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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5T32AG000255/AG/NIA NIH HHS/United States
|
||
</a></li><li class="grant-item"><a
|
||
title="All articles for grant F31 NS073196/NS/NINDS NIH HHS/United States"
|
||
href="/?term=F31+NS073196%2FNS%2FNINDS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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>
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F31 NS073196/NS/NINDS NIH HHS/United States
|
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</a></li><li class="grant-item"><a
|
||
title="All articles for grant GM48661/GM/NIGMS NIH HHS/United States"
|
||
href="/?term=GM48661%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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GM48661/GM/NIGMS NIH HHS/United States
|
||
</a></li></ul><ul id="grants-tail-list" class="list-tail"><li class="grant-item"><a
|
||
title="All articles for grant R01 GM048661/GM/NIGMS NIH HHS/United States"
|
||
href="/?term=R01+GM048661%2FGM%2FNIGMS+NIH+HHS%2FUnited+States%5BGrants+and+Funding%5D&sort=date&sort_order=desc"
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|
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</a></li></ul></div><div class="actions-bar"><button
|
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class="show-all"
|
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Show all 6 grants
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</div>
|
||
|
||
|
||
|
||
|
||
<div id="linkout" class="linkout">
|
||
<h2 class="title">
|
||
LinkOut - more resources
|
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</h2>
|
||
|
||
<ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a
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