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Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes

Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important cellular homeostatic process. This is particularly challenging for neurons because mature acidic lysosomes are relatively enriched in the soma. Although dynein-driven retrograde transport of AVs was suggested, a fundame...

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Autores principales: Cheng, Xiu-Tang, Zhou, Bing, Lin, Mei-Yao, Cai, Qian, Sheng, Zu-Hang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427784/
https://www.ncbi.nlm.nih.gov/pubmed/25940348
http://dx.doi.org/10.1083/jcb.201412046
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author Cheng, Xiu-Tang
Zhou, Bing
Lin, Mei-Yao
Cai, Qian
Sheng, Zu-Hang
author_facet Cheng, Xiu-Tang
Zhou, Bing
Lin, Mei-Yao
Cai, Qian
Sheng, Zu-Hang
author_sort Cheng, Xiu-Tang
collection PubMed
description Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important cellular homeostatic process. This is particularly challenging for neurons because mature acidic lysosomes are relatively enriched in the soma. Although dynein-driven retrograde transport of AVs was suggested, a fundamental question remains how autophagosomes generated at distal axons acquire dynein motors for retrograde transport toward the soma. In this paper, 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 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. Altogether, 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.
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spelling pubmed-44277842015-11-11 Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes Cheng, Xiu-Tang Zhou, Bing Lin, Mei-Yao Cai, Qian Sheng, Zu-Hang J Cell Biol Research Articles Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important cellular homeostatic process. This is particularly challenging for neurons because mature acidic lysosomes are relatively enriched in the soma. Although dynein-driven retrograde transport of AVs was suggested, a fundamental question remains how autophagosomes generated at distal axons acquire dynein motors for retrograde transport toward the soma. In this paper, 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 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. Altogether, 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. The Rockefeller University Press 2015-05-11 /pmc/articles/PMC4427784/ /pubmed/25940348 http://dx.doi.org/10.1083/jcb.201412046 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Cheng, Xiu-Tang
Zhou, Bing
Lin, Mei-Yao
Cai, Qian
Sheng, Zu-Hang
Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
title Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
title_full Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
title_fullStr Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
title_full_unstemmed Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
title_short Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
title_sort axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427784/
https://www.ncbi.nlm.nih.gov/pubmed/25940348
http://dx.doi.org/10.1083/jcb.201412046
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