Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila

Szabolcs Takáts, Péter Nagy, Ágnes Varga, Karolina Pircs, Manuéla Kárpáti, Kata Varga, Attila L. Kovács, Krisztina Hegedus, Gábor Juhász

Research output: Contribution to journalArticle

164 Citations (Scopus)

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 largescale 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.

Original languageEnglish
Pages (from-to)531-539
Number of pages9
JournalJournal of Cell Biology
Volume201
Issue number4
DOIs
Publication statusPublished - May 1 2013

ASJC Scopus subject areas

  • Cell Biology

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