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Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity

Takáts, Szabolcs; Varga, Ágnes; Pircs, Karolina LU and Juhász, Gábor (2015) In Autophagy 11(8). p.15-1209
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... (More)

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.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Animals, Autophagy, Cloning, Molecular, Densitometry, Drosophila Proteins, Drosophila melanogaster, Endocytosis, Gene Expression Regulation, Developmental, Lipids, Lysosomes, Models, Genetic, Mutation, Phagosomes, Phosphorylation, Polymerase Chain Reaction, Qa-SNARE Proteins, Transcription Factors, Up-Regulation, Vesicular Transport Proteins, Journal Article, Research Support, Non-U.S. Gov't
in
Autophagy
volume
11
issue
8
pages
7 pages
publisher
Landes Bioscience
external identifiers
  • scopus:84943741305
ISSN
1554-8635
DOI
10.1080/15548627.2015.1059559
language
English
LU publication?
no
id
a67c98ae-1321-495a-a80b-ed625a1bf158
date added to LUP
2017-03-16 15:12:03
date last changed
2017-07-02 05:00:42
@article{a67c98ae-1321-495a-a80b-ed625a1bf158,
  abstract     = {<p>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.</p>},
  author       = {Takáts, Szabolcs and Varga, Ágnes and Pircs, Karolina and Juhász, Gábor},
  issn         = {1554-8635},
  keyword      = {Animals,Autophagy,Cloning, Molecular,Densitometry,Drosophila Proteins,Drosophila melanogaster,Endocytosis,Gene Expression Regulation, Developmental,Lipids,Lysosomes,Models, Genetic,Mutation,Phagosomes,Phosphorylation,Polymerase Chain Reaction,Qa-SNARE Proteins,Transcription Factors,Up-Regulation,Vesicular Transport Proteins,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {8},
  pages        = {15--1209},
  publisher    = {Landes Bioscience},
  series       = {Autophagy},
  title        = {Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity},
  url          = {http://dx.doi.org/10.1080/15548627.2015.1059559},
  volume       = {11},
  year         = {2015},
}