RRC ID 22712
著者 Takáts S, Nagy P, Varga Á, Pircs K, Kárpáti M, Varga K, Kovács AL, Hegedűs K, Juhász G.
タイトル Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila.
ジャーナル J Cell Biol
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.
巻・号 201(4)
ページ 531-9
公開日 2013-5-13
DOI 10.1083/jcb.201211160
PII jcb.201211160
PMID 23671310
PMC PMC3653357
MeSH Animals Autophagy Cytoplasm / metabolism Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Endosomes / metabolism Gene Expression Regulation Lysosomes / metabolism* Microscopy, Electron Mutation Neurons / metabolism* Phagosomes / physiology* Qa-SNARE Proteins / metabolism* R-SNARE Proteins / metabolism* RNA Interference SNARE Proteins / metabolism*
IF 8.811
引用数 160
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ DGRC#140948 (LL06330) DGRC#115240 (CPTI001775) 11173R-2 1599R-1