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Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila
During autophagy, phagophores capture portions of cytoplasm and form double-membrane autophagosomes to deliver cargo for lysosomal degradation. How autophagosomes gain competence to fuse with late endosomes and lysosomes is not known. In this paper, we show that Syntaxin17 is recruited to the outer...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653357/ https://www.ncbi.nlm.nih.gov/pubmed/23671310 http://dx.doi.org/10.1083/jcb.201211160 |
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author | Takáts, Szabolcs Nagy, Péter Varga, Ágnes Pircs, Karolina Kárpáti, Manuéla Varga, Kata Kovács, Attila L. Hegedűs, Krisztina Juhász, Gábor |
author_facet | Takáts, Szabolcs Nagy, Péter Varga, Ágnes Pircs, Karolina Kárpáti, Manuéla Varga, Kata Kovács, Attila L. Hegedűs, Krisztina Juhász, Gábor |
author_sort | Takáts, Szabolcs |
collection | PubMed |
description | During autophagy, phagophores capture portions of cytoplasm and form double-membrane autophagosomes to deliver cargo for lysosomal degradation. How autophagosomes gain competence to fuse with late endosomes and lysosomes is not known. In this paper, we show that Syntaxin17 is recruited to the outer membrane of autophagosomes to mediate fusion through its interactions with ubisnap (SNAP-29) and VAMP7 in Drosophila melanogaster. Loss of these genes results in accumulation of autophagosomes and a block of autolysosomal degradation during basal, starvation-induced, and developmental autophagy. Viable Syntaxin17 mutant adults show large-scale accumulation of autophagosomes in neurons, severe locomotion defects, and premature death. These mutant phenotypes cannot be rescued by neuron-specific inhibition of caspases, suggesting that caspase activation and cell death do not play a major role in brain dysfunction. Our findings reveal the molecular mechanism underlying autophagosomal fusion events and show that lysosomal degradation and recycling of sequestered autophagosome content is crucial to maintain proper functioning of the nervous system. |
format | Online Article Text |
id | pubmed-3653357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36533572013-11-13 Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila Takáts, Szabolcs Nagy, Péter Varga, Ágnes Pircs, Karolina Kárpáti, Manuéla Varga, Kata Kovács, Attila L. Hegedűs, Krisztina Juhász, Gábor J Cell Biol Research Articles During autophagy, phagophores capture portions of cytoplasm and form double-membrane autophagosomes to deliver cargo for lysosomal degradation. How autophagosomes gain competence to fuse with late endosomes and lysosomes is not known. In this paper, we show that Syntaxin17 is recruited to the outer membrane of autophagosomes to mediate fusion through its interactions with ubisnap (SNAP-29) and VAMP7 in Drosophila melanogaster. Loss of these genes results in accumulation of autophagosomes and a block of autolysosomal degradation during basal, starvation-induced, and developmental autophagy. Viable Syntaxin17 mutant adults show large-scale accumulation of autophagosomes in neurons, severe locomotion defects, and premature death. These mutant phenotypes cannot be rescued by neuron-specific inhibition of caspases, suggesting that caspase activation and cell death do not play a major role in brain dysfunction. Our findings reveal the molecular mechanism underlying autophagosomal fusion events and show that lysosomal degradation and recycling of sequestered autophagosome content is crucial to maintain proper functioning of the nervous system. The Rockefeller University Press 2013-05-13 /pmc/articles/PMC3653357/ /pubmed/23671310 http://dx.doi.org/10.1083/jcb.201211160 Text en © 2013 Takáts et al. 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 Takáts, Szabolcs Nagy, Péter Varga, Ágnes Pircs, Karolina Kárpáti, Manuéla Varga, Kata Kovács, Attila L. Hegedűs, Krisztina Juhász, Gábor Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila |
title | Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila |
title_full | Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila |
title_fullStr | Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila |
title_full_unstemmed | Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila |
title_short | Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila |
title_sort | autophagosomal syntaxin17-dependent lysosomal degradation maintains neuronal function in drosophila |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653357/ https://www.ncbi.nlm.nih.gov/pubmed/23671310 http://dx.doi.org/10.1083/jcb.201211160 |
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