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Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila

Takáts, Szabolcs; Nagy, Péter; Varga, Ágnes; Pircs, Karolina LU ; Kárpáti, Manuéla; Varga, Kata; Kovács, Attila L; Hegedűs, Krisztina and Juhász, Gábor (2013) In Journal of Cell Biology 201(4). p.9-531
Abstract

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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Autophagy, Cytoplasm, Drosophila Proteins, Drosophila melanogaster, Endosomes, Gene Expression Regulation, Lysosomes, Microscopy, Electron, Mutation, Neurons, Phagosomes, Qa-SNARE Proteins, R-SNARE Proteins, RNA Interference, SNARE Proteins, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Cell Biology
volume
201
issue
4
pages
9 pages
publisher
Rockefeller University Press
external identifiers
  • scopus:84878615771
ISSN
0021-9525
DOI
10.1083/jcb.201211160
language
English
LU publication?
no
id
112947ba-9679-4291-bd23-35f9ada8e00e
date added to LUP
2017-03-16 15:28:12
date last changed
2018-12-02 04:49:05
@article{112947ba-9679-4291-bd23-35f9ada8e00e,
  abstract     = {<p>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.</p>},
  author       = {Takáts, Szabolcs and Nagy, Péter and Varga, Ágnes and Pircs, Karolina and Kárpáti, Manuéla and Varga, Kata and Kovács, Attila L and Hegedűs, Krisztina and Juhász, Gábor},
  issn         = {0021-9525},
  keyword      = {Animals,Autophagy,Cytoplasm,Drosophila Proteins,Drosophila melanogaster,Endosomes,Gene Expression Regulation,Lysosomes,Microscopy, Electron,Mutation,Neurons,Phagosomes,Qa-SNARE Proteins,R-SNARE Proteins,RNA Interference,SNARE Proteins,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  number       = {4},
  pages        = {9--531},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Cell Biology},
  title        = {Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila},
  url          = {http://dx.doi.org/10.1083/jcb.201211160},
  volume       = {201},
  year         = {2013},
}