Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Szabolcs Takáts
  • Péter Nagy
  • Ágnes Varga
  • Karolina Pircs
  • Manuéla Kárpáti
  • Kata Varga
  • Attila L Kovács
  • Krisztina Hegedűs
  • Gábor Juhász
Externa organisationer
  • Eötvös Loránd University
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)531-9
Antal sidor9
TidskriftJournal of Cell Biology
Volym201
Utgåva nummer4
StatusPublished - 2013 maj 13
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa