title: Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity.
abstract: The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syx17 (Syntaxin 17), the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosome, a site of its activation. Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals. Thus, Vps16A reduces autophagosome numbers both by indirectly restricting their formation rate and by directly promoting their clearance. In contrast, the loss of Syx17 blocks autophagic flux without affecting the induction step in Drosophila.
authors.affiliation: a Department of Anatomy ; Cell and Developmental Biology; Eötvös Lorand University ; Budapest , Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Takáts
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Varga
authors.forename: Karolina
authors.initials: K
authors.lastname: Pircs
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D003001:Cloning, Molecular; D003720:Densitometry; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004705:Endocytosis; D018507:Gene Expression Regulation, Developmental; D008055:Lipids / Q000737:chemistry; D008247:Lysosomes / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D010588:Phagosomes / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D008055:Lipids; D050765:Qa-SNARE Proteins; C570998:TORC1 protein complex, Drosophila; D014157:Transcription Factors; C507251:VPS16A protein, Drosophila; D033921:Vesicular Transport Proteins
keywords: HOPS; Syntaxin 17; Tor; Vps16A; autophagy; flux; lysosome