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<title>Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-18">Friday, September 18, 2015</time>
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– Poster Session V
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">2:00 – 3:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NINDS</strong></p></div><div class="schedule__description"><p><strong>NEURO-5</strong></p></div></div></div></div><p><strong>FARE Award Winner</strong></p><h2>Authors</h2><ul><li>X Cheng</li><li>B Zhou</li><li>M Lin</li><li>Q Cai</li><li>Z Sheng</li></ul><h2>Abstract</h2><p>During autophagy, an essential catabolic cellular pathway, double-membrane autophagosomes are formed and enclose bulk cytosol and/or organelles. Subsequently, autophagosomes either fuse with late endosomes (LEs), generating a hybrid organelle termed amphisome, or fuse with lysosomes for final degradation. Impairment of this pathway is associated with several neurodegenerative disorders. Thus, efficient degradation of autophagic vacuoles (AVs) via lysosomes is critical for cellular homeostasis. This is particularly challenging for polarized cells, like neurons, which have long processes where mature acidic lysosomes are enriched in the soma, but not in axon terminals. Although dynein-driven retrograde transport of AVs has been suggested, a fundamental question remains-how do autophagosomes that are generated at distal axons acquire dynein motors for retrograde transport to the soma. Here, we demonstrate that late endosome (LE)-loaded dynein-snapin complexes drive AV retrograde transport in axons upon fusion of autophagosomes with LEs into amphisomes. Blocking the fusion between autophagosomes and LEs with syntaxin17 knockdown reduced recruitment of dynein motors to AVs, thus immobilizing them in axons. Deficiency in dynein-snapin coupling impaired AV transport, resulting in AV accumulation in neurites and synaptic terminals. Our study provides the first evidence that autophagosomes recruit dynein through fusion with LEs and reveals a new motor-adaptor sharing mechanism by which neurons may remove distal AVs engulfing aggregated proteins and dysfunctional organelles for efficient degradation in the soma.</p><p><strong>Scientific Focus Area</strong>: Neuroscience</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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