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<meta name="description" content="Oculocerebrorenal syndrome of Lowe is caused by mutation of OCRL1, a phosphatidylinositol 4,5-bisphosphate 5-phosphatase localized at the Golgi apparatus. The cellular role of OCRL1 is unknown, and consequently the mechanism by which loss of OCRL1 function leads to disease is ill defined. Here, we s …"><meta name="keywords" content="pmid:15917292, PMC1182289, doi:10.1091/mbc.e05-02-0120, Research Support, Non-U.S. Gov&#x27;t, Rawshan Choudhury, Aipo Diao, Martin Lowe, Animals, Cell Line, Cell Membrane / metabolism, Chlorocebus aethiops, Clathrin / metabolism*, Cryoelectron Microscopy, Endosomes / drug effects, Endosomes / metabolism*, Humans, Membrane Glycoproteins / metabolism, Oculocerebrorenal Syndrome / genetics*, Phosphoric Monoester Hydrolases / genetics, Phosphoric Monoester Hydrolases / metabolism*, Protein Binding, Protein Transport, RNA Interference, Receptor, IGF Type 2 / metabolism, Shiga Toxin / pharmacology, trans-Golgi Network / drug effects, trans-Golgi Network / metabolism*, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/15917292/"><meta property="og:description" content="Oculocerebrorenal syndrome of Lowe is caused by mutation of OCRL1, a phosphatidylinositol 4,5-bisphosphate 5-phosphatase localized at the Golgi apparatus. The cellular role of OCRL1 is unknown, and consequently the mechanism by which loss of OCRL1 function leads to disease is ill defined. Here, we s …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/15917292/"><meta name="twitter:description" content="Oculocerebrorenal syndrome of Lowe is caused by mutation of OCRL1, a phosphatidylinositol 4,5-bisphosphate 5-phosphatase localized at the Golgi apparatus. The cellular role of OCRL1 is unknown, and consequently the mechanism by which loss of OCRL1 function leads to disease is ill defined. Here, we s …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<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="gr7OoC8CqPp2zKYOOwtwov1cMr4NeMNsxeRT1sBY0qcwtb4ErP6ySDxQkvMZ7nlM">
<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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
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="gr7OoC8CqPp2zKYOOwtwov1cMr4NeMNsxeRT1sBY0qcwtb4ErP6ySDxQkvMZ7nlM">
<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="gr7OoC8CqPp2zKYOOwtwov1cMr4NeMNsxeRT1sBY0qcwtb4ErP6ySDxQkvMZ7nlM">
<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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</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="gr7OoC8CqPp2zKYOOwtwov1cMr4NeMNsxeRT1sBY0qcwtb4ErP6ySDxQkvMZ7nlM">
<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="gr7OoC8CqPp2zKYOOwtwov1cMr4NeMNsxeRT1sBY0qcwtb4ErP6ySDxQkvMZ7nlM">
<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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</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="15917292">
<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://www.molbiolcell.org/doi/10.1091/mbc.e05-02-0120?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub 0pubmed"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=4487&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=15917292&amp;db=pubmed&amp;nlmid=9201390"
title="See full text options at Atypon"
data-ga-category="full_text"
data-ga-action="Atypon"
data-ga-label="15917292"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.molbiolcell.org-pb-assets-images-mbocpubmed.png" alt="Atypon full text link"><span class="text">
Atypon
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/15917292/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=15917292&amp;db=pubmed&amp;nlmid=9201390"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="15917292"
><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="/15917292/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/15917292/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="15917292" 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%2F15917292%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="gr7OoC8CqPp2zKYOOwtwov1cMr4NeMNsxeRT1sBY0qcwtb4ErP6ySDxQkvMZ7nlM"><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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
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data-ga-label="Martin Lowe">Martin Lowe</a></span>
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><sup class="key">1</sup> Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.</li>
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<p>
Oculocerebrorenal syndrome of Lowe is caused by mutation of OCRL1, a phosphatidylinositol 4,5-bisphosphate 5-phosphatase localized at the Golgi apparatus. The cellular role of OCRL1 is unknown, and consequently the mechanism by which loss of OCRL1 function leads to disease is ill defined. Here, we show that OCRL1 is associated with clathrin-coated transport intermediates operating between the trans-Golgi network (TGN) and endosomes. OCRL1 interacts directly with clathrin heavy chain and promotes clathrin assembly in vitro. Interaction with clathrin is not, however, required for membrane association of OCRL1. Overexpression of OCRL1 results in redistribution of clathrin and the cation-independent mannose 6-phosphate receptor (CI-MPR) to enlarged endosomal structures that are defective in retrograde trafficking to the TGN. Depletion of cellular OCRL1 also causes partial redistribution of a CI-MPR reporter to early endosomes. These findings suggest a role for OCRL1 in clathrin-mediated trafficking of proteins from endosomes to the TGN and that defects in this pathway might contribute to the Lowe syndrome phenotype.
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<figure class="figure-item "
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<a class="figure-link"
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itemprop="contentUrl"
aria-describedby="figure-caption-0"
role="button"
data-image-width="432"
data-image-height="488"
data-image-alt="Figure 1."
data-pmc-id="PMC1182289"
data-figure-id="fig1">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/7a5f0eae44dd/zmk0080572340001.gif"
alt="Figure 1." />
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><p> Immunofluorescence localization of OCRL1. Immunofluorescence… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1. </p>
</strong>
<div class="figure-caption-contents"><p> Immunofluorescence localization of OCRL1. Immunofluorescence microscopy of COS-7 cells double labeled with antibodies… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1.
</strong>
<div class="figure-caption-contents">Immunofluorescence localization of OCRL1. Immunofluorescence microscopy of COS-7 cells double labeled with antibodies to OCRL1 (red) and either golgin-97, clathrin heavy chain (CHC), γ-adaptin, or CI-MPR (green). Insets show magnified views of the perinuclear regions indicated by boxes in the merges and indicate puncta that contain both markers. Arrowheads indicate additional puncta outside this region that lack golgin-97 (ac) or contain CHC (df), γ-adaptin (gi), or CI-MPR (jl). Bar, 20 μm.</div>
</figcaption>
</figure>
<figure class="figure-item "
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/4229eddb45c1/zmk0080572340002.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="432"
data-image-height="380"
data-image-alt="Figure 2."
data-pmc-id="PMC1182289"
data-figure-id="fig2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/f4623e953dda/zmk0080572340002.gif"
alt="Figure 2." />
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<strong class="figure-label">
<p> Figure 2. </p>
</strong>
<div class="figure-caption-contents"><p> Colocalization of OCRL1 with endosomal… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2. </p>
</strong>
<div class="figure-caption-contents"><p> Colocalization of OCRL1 with endosomal markers. Immunofluorescence microscopy of COS-7 cells double labeled… </p></div>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2.
</strong>
<div class="figure-caption-contents">Colocalization of OCRL1 with endosomal markers. Immunofluorescence microscopy of COS-7 cells double labeled with antibodies to OCRL1 (green) and either EEA1, TfR, or CD63 (red). Insets show magnified views of the perinuclear regions indicated by boxes in the merges. Arrowheads indicate puncta outside this region that contain EEA1 (ac) or TfR (df) or that lack CD63 (gi). Bar, 20 μm.</div>
</figcaption>
</figure>
<figure class="figure-item "
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data-label-slug="figure-3">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/3e4e94ac9c42/zmk0080572340003.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="404"
data-image-height="170"
data-image-alt="Figure 3."
data-pmc-id="PMC1182289"
data-figure-id="fig3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/aca51cc4f4ab/zmk0080572340003.gif"
alt="Figure 3." />
</a>
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<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 3. </p>
</strong>
<div class="figure-caption-contents"><p> OCRL1 is enriched in clathrin-coated… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3. </p>
</strong>
<div class="figure-caption-contents"><p> OCRL1 is enriched in clathrin-coated vesicles. (ac) HeLa cells stably expressing GFP-OCRL1 were… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3.
</strong>
<div class="figure-caption-contents">OCRL1 is enriched in clathrin-coated vesicles. (ac) HeLa cells stably expressing GFP-OCRL1 were processed for cryoelectron microscopy and labeled with antibodies to GFP (15-nm gold) and clathrin heavy chain (10-nm gold). Arrowheads indicate coated buds and vesicle profiles labeled for both OCRL1 and clathrin. Bar, 200 nm. (d) Crude membranes (CM) and purified clathrin-coated vesicles (CCV) from human placenta were analyzed by SDS-PAGE and Coomassie Blue staining (CBB) or Western blotting (WB) with antibodies to clathrin heavy chain (CHC), γ-adaptin, CI-MPR, GM130, TGN46, or OCRL1. Equal protein (5 μg) was loaded in each lane.</div>
</figcaption>
</figure>
<figure class="figure-item "
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<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/edd1d4c4cb8f/zmk0080572340004.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="432"
data-image-height="543"
data-image-alt="Figure 4."
data-pmc-id="PMC1182289"
data-figure-id="fig4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/a5b7b23d0580/zmk0080572340004.gif"
alt="Figure 4." />
</a>
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<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"><p> OCRL1 interacts directly with clathrin… </p></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"><p> OCRL1 interacts directly with clathrin heavy chain. (a) Full-length OCRL1 or lamin C… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4.
</strong>
<div class="figure-caption-contents">OCRL1 interacts directly with clathrin heavy chain. (a) Full-length OCRL1 or lamin C (control) was tested for interaction with the HD, DD, or TD of clathrin heavy chain in the yeast two-hybrid system. Interaction results in growth on high selection. (b) Pig brain cytosol (PBC) or HeLa membrane extract (HME) were incubated with glutathione beads coupled to GST or GST-clathrin TD and recovered proteins analyzed by Western blotting. (c) PBC or HME was incubated with glutathione beads coupled to GST, GST-golgin-84 head domain (g84), or GST-OCRL1 and recovered proteins analyzed by Western blotting. (d) Purified clathrin was incubated with glutathione beads coupled to GST, GST-golgin-84 head, or GST-OCRL1 and bound proteins analyzed by Coomassie Blue staining. (e) Extracts prepared from parental HeLa cells or cells stably expressing GFP-OCRL1 were incubated with either control antibodies (nonimmune IgG) or antibodies to GFP and bound proteins analyzed by Western blotting with antibodies to clathrin heavy chain (CHC) or OCRL1 (GFP-OCRL1). (f) OCRL1 constructs were tested for interaction with clathrin TD in the yeast two-hybrid system. Growth on high selection indicates interaction.</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/c871/1182289/0f5719b76680/zmk0080572340005.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
data-image-width="404"
data-image-height="183"
data-image-alt="Figure 5."
data-pmc-id="PMC1182289"
data-figure-id="fig5">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/b31e4d08273b/zmk0080572340005.gif"
alt="Figure 5." />
</a>
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 5. </p>
</strong>
<div class="figure-caption-contents"><p> OCRL1 promotes clathrin cage assembly… </p></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"><p> OCRL1 promotes clathrin cage assembly in vitro. (a) OCRL1 (0.9 μM) was incubated… </p></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">OCRL1 promotes clathrin cage assembly in vitro. (a) OCRL1 (0.9 μM) was incubated with or without pure clathrin baskets (0.9 μM, equivalent to 2.7 μM clathrin heavy chains) as indicated. S and T show the high-speed supernatant and total for each sample, respectively. (b) Purified clathrin (1.45 μM) was incubated with increasing concentrations of OCRL1 (0, 0.1, 0.3, 0.6, 1, 1.5, and 2 μM) and dialyzed overnight at pH 6.0 followed by high-speed centrifugation. The supernatant (unassembled) and pellet (assembled) fractions were analyzed by Coomassie Blue staining. (c) Electron microscopy of OCRL1-clathrin baskets formed at 2 μM OCRL1. Bar, 100 nm.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
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<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/4900b98bd8f0/zmk0080572340006.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-5"
role="button"
data-image-width="432"
data-image-height="259"
data-image-alt="Figure 6."
data-pmc-id="PMC1182289"
data-figure-id="fig6">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-5"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/c97082231171/zmk0080572340006.gif"
alt="Figure 6." />
</a>
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<strong class="figure-label">
<p> Figure 6. </p>
</strong>
<div class="figure-caption-contents"><p> Clathrin is not required for… </p></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"><p> Clathrin is not required for association of OCRL1 with Golgi membranes. (a) Immunofluorescence… </p></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">Clathrin is not required for association of OCRL1 with Golgi membranes. (a) Immunofluorescence microscopy of HeLa cells treated with control (lamin A) or clathrin heavy chain (CHC) siRNA for 72 h and labeled with antibodies to CHC and OCRL1. Bar, 20 μm. (b) HeLa cells treated with control (lamin A) or CHC siRNA and transiently transfected with GFP-OCRL1 were analyzed by FRAP at 37°C, and the kinetics of recovery of Golgi-associated GFP-OCRL1 was plotted. (c) FRAP of GFP-OCRL1 at 37°C in transiently transfected HeLa cells depleted of K<sup>+</sup> or treated with hypertonic sucrose.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
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<a class="figure-link"
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itemprop="contentUrl"
aria-describedby="figure-caption-6"
role="button"
data-image-width="432"
data-image-height="369"
data-image-alt="Figure 7."
data-pmc-id="PMC1182289"
data-figure-id="fig7">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-6"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/fef45c2b779d/zmk0080572340007.gif"
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 7. </p>
</strong>
<div class="figure-caption-contents"><p> Overexpression of GFP-OCRL1Δ 237-539 in… </p></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"><p> Overexpression of GFP-OCRL1Δ 237-539 in HeLa cells. Immunofluorescence microscopy of HeLa cells transiently… </p></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">Overexpression of GFP-OCRL1Δ 237-539 in HeLa cells. Immunofluorescence microscopy of HeLa cells transiently transfected with GFP-OCRL1Δ237-539 (green) and labeled with antibodies to GM130, clathrin heavy chain (CHC) or the CI-MPR (red). Arrows indicate structures containing both OCRL1 and GM130. Arrowheads indicate OCRL1 structures that either lack GM130 (ac) or contain CHC (df) or CI-MPR (gi). Transfected cells are indicated with asterisks. Bar, 20 μm.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
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itemprop="contentUrl"
aria-describedby="figure-caption-7"
role="button"
data-image-width="432"
data-image-height="500"
data-image-alt="Figure 8."
data-pmc-id="PMC1182289"
data-figure-id="fig8">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-7"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c871/1182289/5e431276d0b6/zmk0080572340008.gif"
alt="Figure 8." />
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 8. </p>
</strong>
<div class="figure-caption-contents"><p> Overexpression of GFP-OCRL1Δ 237-539 affects… </p></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"><p> Overexpression of GFP-OCRL1Δ 237-539 affects the distribution of γ-adaptin and early endosomal markers.… </p></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">Overexpression of GFP-OCRL1Δ 237-539 affects the distribution of γ-adaptin and early endosomal markers. Immunofluorescence microscopy of HeLa cells transiently transfected with GFP-OCRL1Δ237-539 (green) and labeled with antibodies to γ-adaptin, α-adaptin, TfR, or EEA1 (red). Arrowheads indicate OCRL1 structures that contain TfR (gi) or EEA1 (jl). Transfected cells are indicated with asterisks. Bar, 20 μm.</div>
</figcaption>
</figure>
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<p> Figure 9. </p>
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<div class="figure-caption-contents"><p> GFP-OCRL1 overexpression blocks Shiga toxin… </p></div>
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<p> Figure 9. </p>
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<div class="figure-caption-contents"><p> GFP-OCRL1 overexpression blocks Shiga toxin trafficking from early endosomes to the TGN. HeLa… </p></div>
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Figure 9.
</strong>
<div class="figure-caption-contents">GFP-OCRL1 overexpression blocks Shiga toxin trafficking from early endosomes to the TGN. HeLa cells were either not transfected (control) or transiently transfected with GFP-tagged OCRL1 wild-type (WT) or the Δ237-539 mutant (green) and allowed to internalize STxB for 45 min at 37°C and processed for immunofluorescence microscopy. (a) Cells were labeled with antibodies to STxB (red) and the Golgi marker CTR433 (blue). The asterisk indicates a transfected cell with normal Golgi morphology that is defective in STxB transport to the Golgi. (b) Cells were labeled with antibodies to STxB (red) and TfR (blue). Insets show the merge of the boxed regions between STxB (red) and TfR (blue) with regions of overlap in pink. Bar, 20 μm.</div>
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<p> Figure 10. </p>
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<div class="figure-caption-contents"><p> RNAi-mediated depletion of OCRL1 redistributes… </p></div>
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<p> Figure 10. </p>
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<div class="figure-caption-contents"><p> RNAi-mediated depletion of OCRL1 redistributes CI-MPR and TGN46 to endosomes. HeLa cells stably… </p></div>
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Figure 10.
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<div class="figure-caption-contents">RNAi-mediated depletion of OCRL1 redistributes CI-MPR and TGN46 to endosomes. HeLa cells stably expressing CD8-CI-MPR were treated with no siRNA, control siRNA (lamin A), or OCRL1 siRNA for 72 h and analyzed by Western blotting (a) or immunofluorescence microscopy (bd). (b) Cells were labeled with antibodies to OCRL1 (our unpublished data) and golgin-97, TGN46, or CD8 (CD8-CI-MPR). Images are of cells with no detectable OCRL1 staining. (c) Cells were labeled with antibodies to TGN46 and CD8 (CD8-CI-MPR). (d) Cells were double labeled with antibodies to TGN46 and either EEA1 (top) or TfR (bottom). Bar, 20 μm.</div>
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