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|
||
|
||
<a href="/clipboard/"
|
||
class="search-input-link clipboard-link hidden"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<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%2F22753417%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%2F22753417%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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
</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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
|
||
|
||
<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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
<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: 22753417 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 22753417"/>
|
||
<input type="hidden" name="email-subject-hash" value="b5b633d4bf94db2f5a3b56aa9b3c0693b37ce7dc08d4b45c095187135bdbd624"/>
|
||
</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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
|
||
|
||
<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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
|
||
|
||
<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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
<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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
|
||
|
||
<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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ">
|
||
|
||
<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="22753417">
|
||
<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/S0021-9258(20)68431-9"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=22753417&db=pubmed&nlmid=2985121R"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="22753417"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.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/22753417/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=22753417&db=pubmed&nlmid=2985121R"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="22753417"
|
||
><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="/22753417/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/22753417/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="22753417" 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%2F22753417%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="EdKBNs0KZ6fvqW5ta6J8EAWU4WOHdy2wV0uGqit6zH2ZknbjNpma8IsyC0wT69AQ"><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"
|
||
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A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2
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A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2
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Hyperekplexia or startle disease is characterized by an exaggerated startle response, evoked by tactile or auditory stimuli, producing hypertonia and apnea episodes. Although rare, this orphan disorder can have serious consequences, including sudden infant death. Dominant and recessive mutations in the human glycine receptor (GlyR) α1 gene (GLRA1) are the major cause of this disorder. However, recessive mutations in the presynaptic Na(+)/Cl(-)-dependent glycine transporter GlyT2 gene (SLC6A5) are rapidly emerging as a second major cause of startle disease. In this study, systematic DNA sequencing of SLC6A5 revealed a new dominant GlyT2 mutation: pY705C (c.2114A→G) in transmembrane domain 11, in eight individuals from Spain and the United Kingdom. Curiously, individuals harboring this mutation show significant variation in clinical presentation. In addition to classical hyperekplexia symptoms, some individuals had abnormal respiration, facial dysmorphism, delayed motor development, or intellectual disability. We functionally characterized this mutation using molecular modeling, electrophysiology, [(3)H]glycine transport, cell surface expression, and cysteine labeling assays. We found that the introduced cysteine interacts with the cysteine pair Cys-311-Cys-320 in the second external loop of GlyT2. This interaction impairs transporter maturation through the secretory pathway, reduces surface expression, and inhibits transport function. Additionally, Y705C presents altered H(+) and Zn(2+) dependence of glycine transport that may affect the function of glycinergic neurotransmission in vivo.
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<div class="figure-caption-contents"><b> Pedigree of families 1 (… </b></div>
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<div class="figure-caption-contents"><b> Pedigree of families 1 ( <i> A </i> ), 2 ( <i> B </i> ), and 3… </b></div>
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<div class="figure-caption-contents"><b>Pedigree of families 1 (<i>A</i>), 2 (<i>B</i>), and 3 (<i>C</i>).</b> Individuals are numbered according to their position in the pedigree lines as I, II, III, and IV, and then each individual from left to right as 1, 2, 3, etc. Males and females are represented by <i>squares</i> and <i>circles</i>, respectively. <i>Shaded symbols</i> represent individuals with the Y705C mutation or who are/were affected, with clinical signs observed.</div>
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<div class="figure-caption-contents"><b> Genetic and structural analysis of… </b></div>
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<div class="figure-caption-contents"><b> Genetic and structural analysis of the Y705C mutant. </b> <i> A </i> , partial sequences of…</div>
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<div class="figure-caption-contents"><b>Genetic and structural analysis of the Y705C mutant.</b>
|
||
<i>A</i>, partial sequences of exon 15 from control and patient 1 DNAs, respectively. Note the heterozygous single-nucleotide polymorphism c.2114A→G changes the codon T<underline>A</underline>T to T<underline>G</underline>T, resulting in a pY705C substitution in GlyT2. <i>B</i>, molecular model of GlyT2 showing the localization of Tyr-705 in TM11. <i>C</i>, phylogenetic comparison of TM11 regions of GlyT2 containing the amino acid Tyr-705 (in <i>red</i>). <i>D</i>, sequence alignment of GlyT2 TM11 region in human SLC6 family members. Sequences were obtained from NCBI (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov">www.ncbi.nlm.nih.gov</ext-link>) and were aligned using ClustalW software and MUSCLE alignment server.</div>
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data-image-alt="FIGURE 3."
|
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|
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/688e91426b56/zbc0361220210003.gif"
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<p> FIGURE 3. </p>
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<div class="figure-caption-contents"><b> Glycine transport and electrophysiological characterization… </b></div>
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<p> FIGURE 3. </p>
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|
||
<div class="figure-caption-contents"><b> Glycine transport and electrophysiological characterization of wild-type GlyT2 and the Y705C mutant. </b> <i> A… </i></div>
|
||
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||
|
||
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FIGURE 3.
|
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||
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|
||
<div class="figure-caption-contents"><b>Glycine transport and electrophysiological characterization of wild-type GlyT2 and the Y705C mutant.</b>
|
||
<i>A</i>, COS7 cells expressing the indicated transporters were assayed for <sup>3</sup>[H]glycine transport during 10 min in HBS containing 150 m<sc>m</sc> NaCl in the presence of increasing glycine concentrations from 0.5 to 1 m<sc>m</sc>. Experimental data were fitted to hyperbolae. Kinetic parameters are indicated on the graph. *, significantly different from wild-type GlyT2, <i>p</i> < 0.05 in Student's <i>t</i> test. <i>B</i>, inward currents evoked by glycine in representative oocytes expressing wild-type GlyT2 or the Y705C mutant. The cells were voltage-clamped at −40 mV, and 1 m<sc>m</sc> glycine was superfused for the period indicated by the <i>solid bar</i>. Histogram represents arithmetic means ± S.E. (<i>n</i> = 5–10 oocytes) of normalized inward currents for wild-type GlyT2 and the Y705C mutant. *, significantly different from wild-type GlyT2, <i>p</i> < 0.05 in Student's <i>t</i> test. <i>C</i>, current-voltage plots of the glycine-mediated inward currents of wild-type GlyT2 and Y705C mutant determined by subtracting, in each case, the currents observed in the absence of glycine.</div>
|
||
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|
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aria-describedby="figure-caption-3"
|
||
role="button"
|
||
data-image-width="805"
|
||
data-image-height="882"
|
||
data-image-alt="FIGURE 4."
|
||
data-pmc-id="PMC3436537"
|
||
data-figure-id="F4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/26872c885332/zbc0361220210004.gif"
|
||
alt="FIGURE 4." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="805">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="882">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Cell and plasma membrane expression… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Cell and plasma membrane expression of wild-type GlyT2 and Y705C. </b> <i> A </i> , immunofluorescence…</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.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Cell and plasma membrane expression of wild-type GlyT2 and Y705C.</b>
|
||
<i>A</i>, immunofluorescence quantification of plasma membrane transporters. Wild-type EGFP-tagged GlyT2 or Y705C expressed in MDCK cells for 48 h were immunolabeled for the plasma membrane marker E-cadherin (<i>E-cad</i>). Two channel confocal images were obtained (<i>green</i> for GlyT2 and <i>red</i> for E-cadherin), and regions occupied by E-cadherin were taken as plasma membrane and regions inside the cadherin staining were taken as intracellular, using the Image J ROI manager. After applying an automatic threshold to adjust images, the fluorescence intensity was measured separately for membrane and intracellular regions, and the percentage of transporter in plasma membrane was calculated (histogram). This process was performed at least in 150 cells/condition. *, <i>p</i> < 0.05 values calculated using Student's <i>t</i> test by comparing wild-type GlyT2 with the Y705C mutant. <i>B</i>, COS7 cells expressing wild-type GlyT2 or Y705C mutant were subjected to biotinylation as described under “Experimental Procedures.” 8 μg of total (<i>lanes T</i>) and nonbiotinylated proteins (<i>lanes NB</i>) and 24 μg of biotinylated proteins (<i>lanes B</i>) were subjected to Western blotting for GlyT2 detection, and the membranes were reprobed for calnexin immunoreactivity as a loading control. <i>Lower panel</i>, densitometric analysis. <i>Black bars</i>, total transporter that was biotin-labeled (<i>B</i> as a % of <i>T</i>) as percentage of that of wild-type GlyT2. <i>Open bars</i>, mature/immature transporter ratio (100 kDa/75 kDa) as a percentage of the ratio (100 kDa/75 kDa) for wild-type GlyT2. *, <i>p</i> < 0.05 in Student's <i>t</i> test. <i>C</i>, MDCK cells expressing wild-type EGFP-tagged GlyT2 or Y705C were immunolabeled for calnexin (<i>CNX</i>, endoplasmic reticulum marker) or early endosome antigen 1 (<i>EEA1</i>, early endosome marker). No significantly difference in co-localization was observed. <i>D</i>, MDCK cells transfected with wild-type EGFP-tagged GlyT2 or Y705C were plated on cell culture filter inserts and grown to confluence. Samples were examined by laser scanning confocal microscopy. <i>Left panel</i>, en face views. <i>Right panel</i>, <i>x-z</i> cross-sections. The <i>x-z</i> cross-sections are derived from the indicated transept lines.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="4"
|
||
data-label-slug="figure-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/39bca15663bd/zbc0361220210005.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-4"
|
||
role="button"
|
||
data-image-width="492"
|
||
data-image-height="407"
|
||
data-image-alt="FIGURE 5."
|
||
data-pmc-id="PMC3436537"
|
||
data-figure-id="F5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/b443c1730d8b/zbc0361220210005.gif"
|
||
alt="FIGURE 5." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="492">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="407">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Substitution analysis of Tyr-705 and… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Substitution analysis of Tyr-705 and effect of DTT on glycine transport. </b> Transiently transfected…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 5.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Substitution analysis of Tyr-705 and effect of DTT on glycine transport.</b> Transiently transfected COS7 cells expressing wild-type GlyT2 or mutants with the indicated amino acids at position 705, were subjected to biotinylation as described in Fig. 4 to determine plasma membrane expression (<i>A</i>) or treated with vehicle or 12 m<sc>m</sc> DTT (<i>B</i>) or 2.5 m<sc>m</sc> DTT (<i>D</i>) or the specified concentrations of the indicated reducing agents (<i>C</i>) and then assayed for [<sup>3</sup>H]glycine transport. In <i>B</i>, * indicates significantly different from wild-type GlyT2, <i>p</i> < 0.05 in Student's <i>t</i> test. In <i>C</i> and <i>D</i>, ** indicates <i>p</i> < 0.01, and * indicates <i>p</i> < 0.05 by analysis of variance. <i>Lanes T</i>, total proteins; <i>lanes NB</i>, nonbiotinylated proteins; <i>lanes B</i>, biotinylated proteins.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="5"
|
||
data-label-slug="figure-6">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/9c17209236ce/zbc0361220210006.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-5"
|
||
role="button"
|
||
data-image-width="514"
|
||
data-image-height="466"
|
||
data-image-alt="FIGURE 6."
|
||
data-pmc-id="PMC3436537"
|
||
data-figure-id="F6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/9d1cc69e4318/zbc0361220210006.gif"
|
||
alt="FIGURE 6." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="514">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="466">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 6. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Effect of DTT on Y705C… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 6. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Effect of DTT on Y705C plasma membrane expression. </b> COS7 cells expressing wild-type GlyT2…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 6.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Effect of DTT on Y705C plasma membrane expression.</b> COS7 cells expressing wild-type GlyT2 or Y705C were treated with 12 m<sc>m</sc> DTT at 22 °C for the indicated times and then assayed for [<sup>3</sup>H]glycine transport for 10 min (<i>A</i>) or subjected to sulfo-NHS-SS-biotinylation as described under “Experimental Procedures” (<i>B</i>). <i>A</i>, transport data are expressed as percentages of wild-type GlyT2 transport activity, which was 2.8 ± 0.3 nmol of Gly/mg of protein/10 min. *, significantly different from no DTT, <i>p</i> < 0.05 in Student's <i>t</i> test. <i>B</i>, <i>upper panel</i>, Western blot for GlyT2 detection of a SDS-PAGE loaded with 8 μg of total (<i>lanes T</i>) and nonbiotinylated proteins (<i>lanes N</i>) and 24 μg of biotinylated proteins (<i>lanes B</i>). <i>Lower panel</i>, densitometric analysis. *, significantly different from no DTT, <i>p</i> < 0.05 in Student's <i>t</i> test. <i>C</i>, MDCK cells expressing wild-type EGFP-tagged GlyT2 or Y705C were treated for 30 min with 12 m<sc>m</sc> DTT, placed on ice to stop trafficking, and immunolabeled for the plasma membrane marker E-cadherin (<i>E-cad</i>). <i>D</i>, co-localization of transporter and marker was performed as described for Fig. 4. *, <i>p</i> < 0.05 values calculated using Student's <i>t</i> test by comparing wild-type GlyT2 with the Y705C mutant.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="6"
|
||
data-label-slug="figure-7">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/3311985c514e/zbc0361220210007.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-6"
|
||
role="button"
|
||
data-image-width="805"
|
||
data-image-height="1212"
|
||
data-image-alt="FIGURE 7."
|
||
data-pmc-id="PMC3436537"
|
||
data-figure-id="F7">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/5b9ea27d88aa/zbc0361220210007.gif"
|
||
alt="FIGURE 7." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="805">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1212">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 7. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> MTSEA-biotin labeling and transport activity… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 7. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> MTSEA-biotin labeling and transport activity of Y705C and GlyT2 cysteine mutants. </b> <i> A </i> ,…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 7.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>MTSEA-biotin labeling and transport activity of Y705C and GlyT2 cysteine mutants.</b>
|
||
<i>A</i>, COS7 cells expressing wild-type GlyT2 or Y705C were treated with vehicle or 50 m<sc>m</sc>
|
||
<i>N</i>-ethylmaleimide (<i>NEM</i>) for 10 min, washed, and treated with HBS or 12 m<sc>m</sc> DTT in HBS for 30 min, washed, and subjected to MTSEA-biotinylation as described under “Experimental Procedures.” <i>Upper panel</i>, Western blot for GlyT2 detection of a SDS-PAGE loaded with 10 μg of total (<i>lanes T</i>) and 100 μg of biotinylated proteins (<i>lanes B</i>). <i>Lower panel</i>, densitometric analysis of the percentage of total transporter (<i>B</i> as a % of <i>T</i>) that was MTSEA-biotin-labeled in each condition as percentage of control wild-type GlyT2. ***, Significantly different from wild-type GlyT2, <i>p</i> < 0.001 in Student's <i>t</i> test. <i>B</i>, <i>upper panel</i>, molecular model of GlyT2 showing the localization of Tyr-705 and some of the endogenous cysteines (<i>black</i>). <i>Lower panel</i>, location of the Cys-311–Cys-320 pair in the second external loop as compared with Cys-705 on schematic GlyT2 secondary structure. <i>C</i> and <i>D</i>, effect of DTT on glycine transport by cysteine to serine mutants in the background of wild-type GlyT2 or the Y705C mutant. COS7 cells expressing wild-type GlyT2, Y705C, cysteine to serine mutants (<i>CXS</i>), or Y705C/cysteine to serine double mutants (<i>CXS/Y705C</i>) for 48 h were assayed for [<sup>3</sup>H]glycine transport for 10 min after being treated with vehicle (<i>C</i>) or with 12 m<sc>m</sc> DTT at 22 °C for 5 min (<i>D</i>). <i>E</i>, COS7 cells expressing the indicated transporters were treated with vehicle (−DTT) or DTT (+DTT) for 30 min, washed, and MTSEA-biotin-labeled; streptavidin-agarose bound proteins were run in nonreducing (−<i>DTT</i>) or reducing (+<i>DTT</i>) SDS-PAGE and subjected to Western blotting as above. <i>F</i>, densitometric analysis of the percentage of total transporter that was MTSEA-biotin-labeled in each condition. For clarity, this was expressed as percentage of the respective wild-type GlyT2 in each condition. Significantly different from the Y705C single mutant: *, <i>p</i> < 0.05; **, <i>p</i> < 0.01 in Student's <i>t</i> test.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="7"
|
||
data-label-slug="figure-8">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/9fbd6060db42/zbc0361220210008.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-7"
|
||
role="button"
|
||
data-image-width="805"
|
||
data-image-height="976"
|
||
data-image-alt="FIGURE 8."
|
||
data-pmc-id="PMC3436537"
|
||
data-figure-id="F8">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-7"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f5a/3436537/6d8834abaef5/zbc0361220210008.gif"
|
||
alt="FIGURE 8." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="805">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="976">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 8. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Surface labeling and co-expression of… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 8. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Surface labeling and co-expression of Y705C and GlyT2 cysteine mutants. </b> <i> A </i> , COS7…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 8.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Surface labeling and co-expression of Y705C and GlyT2 cysteine mutants.</b>
|
||
<i>A</i>, COS7 cells expressing the indicated transporters were treated with vehicle (−<i>DTT</i>) or DTT (+<i>DTT</i>) for 30 min, washed, and subjected to NHS-SS-biotinylation as in Fig. 4<i>B. Lanes T</i>, total proteins; <i>lanes B</i>, biotinylated proteins. <i>B</i>, densitometric analysis of three blots as in <i>A</i> showing the immunoreactivity of 200-kDa dimers (<i>band</i> marked with <i>asterisk</i> in <i>A</i>) normalized by the total transporter immunoreactivity. ***, significantly different from the respective single mutant, <i>p</i> < 0.01 in Student's <i>t</i> test. <i>C</i>, effect of wild-type GlyT2 and Y705C on transporter expression. COS7 cells expressing wild-type GlyT2 or Y705C tagged with EGFP as described in Ref. at the indicated ratios (increasing mutant cDNA) were assayed for [<sup>3</sup>H]glycine transport and in parallel subjected to NHS-SS-biotinylation as described under “Experimental Procedures” except anti-EGFP antibody was used for the Western blots. <i>D</i>, effect of the expression of Y705C on EGFP-GlyT2 expression (densitometric analysis of blots as in <i>C</i>) and transport activity. <i>E</i>, effect of the expression of Y705C on EGFP-GlyT2 surface expression.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
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<p> FIGURE 9. </p>
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<div class="figure-caption-contents"><b> Effect of pH on glycine… </b></div>
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<strong class="figure-label">
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<p> FIGURE 9. </p>
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</strong>
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|
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|
||
<div class="figure-caption-contents"><b> Effect of pH on glycine transport by wild-type GlyT2 and the Tyr-705 mutant.… </b></div>
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</div>
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FIGURE 9.
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</strong>
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||
<div class="figure-caption-contents"><b>Effect of pH on glycine transport by wild-type GlyT2 and the Tyr-705 mutant.</b> Transiently transfected COS7 cells expressing wild-type GlyT2 or mutants with the indicated amino acid substitutions at position 705 were assayed for [<sup>3</sup>H]glycine transport for 5 min in HBS containing 150 (<i>A</i> and <i>C</i>) or 75 (<i>B</i> and <i>C</i>) m<sc>m</sc> NaCl at 10 μ<sc>m</sc> or the indicated final glycine concentration and pH. Control GlyT2 transport values at pH 7.4 were 1.4 ± 0.2 and 0.73 ± 0.1 nmol of Gly/mg of protein/5 min at 150 and 75 m<sc>m</sc> NaCl, respectively. Mean pH change was significantly different from wild-type GlyT2. *, <i>p</i> < 0.05 by analysis of variance with Dunnett's post hoc test. <i>C</i>, kinetics of glycine transport at low pH. COS7 cells expressing wild-type GlyT2, the Y705C mutant, or the indicated combination of the respective cDNAs were assayed for [<sup>3</sup>H]glycine transport at pH 7.4 or 5.4 for 5 min in HBS containing 150 or 75 m<sc>m</sc> NaCl and glycine concentrations increasing from 0.5 μ<sc>m</sc> to 1 m<sc>m</sc>. Experimental data were fitted to hyperbolae. The kinetic parameters are indicated on the graphs. Mean pH change significantly different from wild-type GlyT2. *, <i>p</i> < 0.05 in Student's <i>t</i> test.</div>
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<p> FIGURE 10. </p>
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<div class="figure-caption-contents"><b> Effect of Zn <sup> 2+ </sup> on… </b></div>
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<strong class="figure-label">
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<p> FIGURE 10. </p>
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</strong>
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||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Effect of Zn <sup> 2+ </sup> on glycine transport by wild-type GlyT2 and the Y705C… </b></div>
|
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|
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</div>
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<figcaption id="figure-caption-9" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
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FIGURE 10.
|
||
</strong>
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||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Effect of Zn<sup>2+</sup> on glycine transport by wild-type GlyT2 and the Y705C mutant.</b> Transiently transfected COS7 cells expressing wild-type GlyT2, the Y705C mutant, or the indicated combinations of the respective cDNAs were assayed for [<sup>3</sup>H]glycine transport for 5 min in HBS containing 75 m<sc>m</sc> NaCl at the indicated pH and 10 μ<sc>m</sc> final glycine concentration (<i>A</i> and <i>B</i>) or increasing glycine concentrations (<i>C</i>) in the presence of the indicated ZnCl concentrations (<i>A–C</i>). NaCl was isotonically substituted by choline chloride. <i>B</i>, dose-response data were fit to logistic curves. <i>C</i>, transport data were fitted to hyperbolae, and kinetic parameters were obtained from the best fit. Mean change significantly different from wild-type GlyT2. *, <i>p</i> < 0.05 in Student's <i>t</i> test.</div>
|
||
|
||
|
||
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||
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Aragón C., López-Corcuera B. (2003) Structure, function and regulation of glycine neurotransporters. Eur. J. Pharmacol. 479, 249–262
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aria-label="Dropdown menu for keyword Research Support, Non-U.S. Gov't"><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=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&keyword="Research Support, Non-U.S. Gov't"[pt]"
|
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data-ga-category="search"
|
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data-ga-action="pub_type"
|
||
data-ga-label="Research Support, Non-U.S. Gov't">
|
||
Search in PubMed
|
||
</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
||
href="https://www.ncbi.nlm.nih.gov/mesh?term=Research+Support%2C+Non-U.S.+Gov%27t"
|
||
data-ga-category="search_mesh"
|
||
data-ga-action="pub_type_link"
|
||
data-ga-label="Research Support, Non-U.S. Gov't">
|
||
Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
||
data-search-term=""Research Support, Non-U.S. Gov't"[pt]"
|
||
data-ga-category="search"
|
||
data-ga-action="add_to_search"
|
||
data-ga-label=""Research Support, Non-U.S. Gov't"[pt]"
|
||
href="#">
|
||
Add to Search
|
||
</a></li></ul></div></div></div></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="mesh-terms" class="mesh-terms keywords-section">
|
||
<h2 class="title">
|
||
MeSH terms
|
||
</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 Amino Acid Substitution"
|
||
tabindex="0"
|
||
aria-controls="keyword-actions-mesh-terms-0"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Amino Acid Substitution
|
||
</button><div id="keyword-actions-mesh-terms-0"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Amino Acid Substitution"><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=%22Amino+Acid+Substitution%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Amino+Acid+Substitution%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Amino Acid Substitution"[MeSH]"
|
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data-ga-category="search"
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data-ga-action="mesh_term"
|
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data-ga-label="Amino Acid Substitution">
|
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Search in PubMed
|
||
</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Amino+Acid+Substitution"
|
||
data-ga-category="search_mesh"
|
||
data-ga-action="mesh_term_link"
|
||
data-ga-label="Amino Acid Substitution">
|
||
Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
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data-search-term=""Amino Acid Substitution"[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=""Amino Acid Substitution"[MeSH]"
|
||
href="#">
|
||
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 Animals"
|
||
tabindex="0"
|
||
aria-controls="keyword-actions-mesh-terms-1"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Animals
|
||
</button><div id="keyword-actions-mesh-terms-1"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Animals"><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=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Animals"[MeSH]"
|
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data-ga-category="search"
|
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data-ga-action="mesh_term"
|
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data-ga-label="Animals">
|
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Search in PubMed
|
||
</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
||
href="https://www.ncbi.nlm.nih.gov/mesh?term=Animals"
|
||
data-ga-category="search_mesh"
|
||
data-ga-action="mesh_term_link"
|
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data-ga-label="Animals">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
||
data-search-term=""Animals"[MeSH]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Animals"[MeSH]"
|
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href="#">
|
||
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 Female"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-2"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Female
|
||
</button><div id="keyword-actions-mesh-terms-2"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Female"><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=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Female"[MeSH]"
|
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data-ga-category="search"
|
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data-ga-action="mesh_term"
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data-ga-label="Female">
|
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
||
href="https://www.ncbi.nlm.nih.gov/mesh?term=Female"
|
||
data-ga-category="search_mesh"
|
||
data-ga-action="mesh_term_link"
|
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data-ga-label="Female">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
||
data-search-term=""Female"[MeSH]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Female"[MeSH]"
|
||
href="#">
|
||
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 major"
|
||
aria-label="Toggle dropdown menu for keyword Genes, Dominant*"
|
||
tabindex="0"
|
||
aria-controls="keyword-actions-mesh-terms-major-3"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Genes, Dominant*
|
||
</button><div id="keyword-actions-mesh-terms-major-3"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Genes, Dominant*"><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=%22Genes%2C+Dominant%22%5BMAJR%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Genes%2C+Dominant%22%5BMAJR%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Genes, Dominant"[MAJR]"
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data-ga-category="search"
|
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data-ga-action="mesh_term"
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data-ga-label="Genes, Dominant*">
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
||
href="https://www.ncbi.nlm.nih.gov/mesh?term=Genes%2C+Dominant"
|
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data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
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data-ga-label="Genes, Dominant*">
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
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role="button"
|
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data-search-term=""Genes, Dominant"[MAJR]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Genes, Dominant"[MAJR]"
|
||
href="#">
|
||
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 major"
|
||
aria-label="Toggle dropdown menu for keyword Genetic Diseases, Inborn* / genetics"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-4"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
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Genetic Diseases, Inborn* / genetics
|
||
</button><div id="keyword-actions-mesh-terms-major-4"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
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aria-label="Dropdown menu for keyword Genetic Diseases, Inborn* / genetics"><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=%22Genetic+Diseases%2C+Inborn%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Genetic+Diseases%2C+Inborn%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Genetic Diseases, Inborn/genetics"[MAJR]"
|
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data-ga-category="search"
|
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data-ga-action="mesh_term"
|
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data-ga-label="Genetic Diseases, Inborn* / genetics">
|
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Genetic+Diseases%2C+Inborn"
|
||
data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
|
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data-ga-label="Genetic Diseases, Inborn* / genetics">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
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data-search-term=""Genetic Diseases, Inborn/genetics"[MAJR]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Genetic Diseases, Inborn/genetics"[MAJR]"
|
||
href="#">
|
||
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 major"
|
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aria-label="Toggle dropdown menu for keyword Genetic Diseases, Inborn* / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-5"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Genetic Diseases, Inborn* / metabolism
|
||
</button><div id="keyword-actions-mesh-terms-major-5"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Genetic Diseases, Inborn* / metabolism"><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=%22Genetic+Diseases%2C+Inborn%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Genetic+Diseases%2C+Inborn%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Genetic Diseases, Inborn/metabolism"[MAJR]"
|
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data-ga-category="search"
|
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data-ga-action="mesh_term"
|
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data-ga-label="Genetic Diseases, Inborn* / metabolism">
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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=Genetic+Diseases%2C+Inborn"
|
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data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
|
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data-ga-label="Genetic Diseases, Inborn* / metabolism">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
||
data-search-term=""Genetic Diseases, Inborn/metabolism"[MAJR]"
|
||
data-ga-category="search"
|
||
data-ga-action="add_to_search"
|
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data-ga-label=""Genetic Diseases, Inborn/metabolism"[MAJR]"
|
||
href="#">
|
||
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 Glycine / genetics"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-6"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Glycine / genetics
|
||
</button><div id="keyword-actions-mesh-terms-6"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Glycine / genetics"><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=%22Glycine%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Glycine%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&mesh="Glycine/genetics"[MeSH]"
|
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data-ga-category="search"
|
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data-ga-action="mesh_term"
|
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data-ga-label="Glycine / genetics">
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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=Glycine"
|
||
data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
|
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data-ga-label="Glycine / genetics">
|
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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=""Glycine/genetics"[MeSH]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Glycine/genetics"[MeSH]"
|
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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 / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-7"
|
||
aria-expanded="false"
|
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data-pinger-ignore>
|
||
Glycine / metabolism
|
||
</button><div id="keyword-actions-mesh-terms-7"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Glycine / 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=%22Glycine%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Glycine%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Glycine/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-label="Glycine / metabolism">
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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=Glycine"
|
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data-ga-category="search_mesh"
|
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data-ga-action="mesh_term_link"
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data-ga-label="Glycine / metabolism">
|
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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/metabolism"[MeSH]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Glycine/metabolism"[MeSH]"
|
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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 major"
|
||
aria-label="Toggle dropdown menu for keyword Glycine Plasma Membrane Transport Proteins* / genetics"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-8"
|
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aria-expanded="false"
|
||
data-pinger-ignore>
|
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Glycine Plasma Membrane Transport Proteins* / genetics
|
||
</button><div id="keyword-actions-mesh-terms-major-8"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
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aria-label="Dropdown menu for keyword Glycine Plasma Membrane Transport Proteins* / genetics"><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=%22Glycine+Plasma+Membrane+Transport+Proteins%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Glycine+Plasma+Membrane+Transport+Proteins%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Glycine Plasma Membrane Transport Proteins/genetics"[MAJR]"
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data-ga-category="search"
|
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data-ga-action="mesh_term"
|
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data-ga-label="Glycine Plasma Membrane Transport Proteins* / genetics">
|
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Glycine+Plasma+Membrane+Transport+Proteins"
|
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data-ga-category="search_mesh"
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data-ga-label="Glycine Plasma Membrane Transport Proteins* / genetics">
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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=""Glycine Plasma Membrane Transport Proteins/genetics"[MAJR]"
|
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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 Plasma Membrane Transport Proteins/genetics"[MAJR]"
|
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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 major"
|
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aria-label="Toggle dropdown menu for keyword Glycine Plasma Membrane Transport Proteins* / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-9"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
||
Glycine Plasma Membrane Transport Proteins* / metabolism
|
||
</button><div id="keyword-actions-mesh-terms-major-9"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Glycine Plasma Membrane Transport Proteins* / metabolism"><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=%22Glycine+Plasma+Membrane+Transport+Proteins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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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="Dropdown menu for keyword Humans"><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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</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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Nerve Tissue Proteins* / genetics
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Add to Search
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Nerve Tissue Proteins* / metabolism
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hidden
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Search in PubMed
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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 major"
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aria-label="Toggle dropdown menu for keyword Nervous System Diseases* / genetics"
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aria-expanded="false"
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Nervous System Diseases* / genetics
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</button><div id="keyword-actions-mesh-terms-major-16"
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hidden
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aria-label="Dropdown menu for keyword Nervous System Diseases* / 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=%22Nervous+System+Diseases%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Nervous+System+Diseases%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Nervous System Diseases/genetics"[MAJR]"
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Search in PubMed
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Search in MeSH
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data-search-term=""Nervous System Diseases/genetics"[MAJR]"
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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 major"
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Nervous System Diseases* / metabolism
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</button><div id="keyword-actions-mesh-terms-major-17"
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hidden
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Search in PubMed
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Search in 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-expanded="false"
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data-pinger-ignore>
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Presynaptic Terminals
|
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</button><div id="keyword-actions-mesh-terms-18"
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hidden
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aria-label="Dropdown menu for keyword Presynaptic Terminals"><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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Search in MeSH
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data-pinger-ignore>
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Protein Transport / genetics
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Search in PubMed
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<div id="related-links" class="related-links">
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<h2 class="title">
|
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Related information
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</h2>
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<ul class="related-links-list"><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&from_uid=22753417"
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ClinVar
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Gene
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Gene (GeneRIF)
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</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=22753417"
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MedGen
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</a></li><li><a title="Published protein sequences" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein&from_uid=22753417"
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Protein
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Protein (RefSeq)
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Grants and funding
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LinkOut - more resources
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href="https://www.nih.gov/">NIH</a>
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