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Takáts, S., Nagy, P., Varga, A., Pircs, K., Kárpáti, M., Varga, K., Kovács, A.L., Hegedus, K., Juhász, G. (2013). Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila.  J. Cell Biol. 201(4): 531--539.
FlyBase ID
FBrf0221516
Publication Type
Research paper
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 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.

PubMed ID
PubMed Central ID
PMC3653357 (PMC) (EuropePMC)
Related Publication(s)
Review

Evolutionarily conserved role and physiological relevance of a STX17/Syx17 (syntaxin 17)-containing SNARE complex in autophagosome fusion with endosomes and lysosomes.
Hegedűs et al., 2013, Autophagy 9(10): 1642--1646 [FBrf0224628]

Note

Route to destruction: autophagosomes SNARE lysosomes.
Krämer, 2013, J. Cell Biol. 201(4): 495--497 [FBrf0222082]

A genetic model with specifically impaired autophagosome-lysosome fusion.
Takáts and Juhász, 2013, Autophagy 9(8): 1251--1252 [FBrf0222389]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
    Data From Reference