Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity
(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.
(Less)
- author
- Takáts, Szabolcs ; Varga, Ágnes ; Pircs, Karolina LU and Juhász, Gábor
- organization
- publishing date
- 2015
- type
- 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
-
- pmid:26061715
- 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
- 2024-10-14 02:47:40
@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}}, 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}}, 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}}, doi = {{10.1080/15548627.2015.1059559}}, volume = {{11}}, year = {{2015}}, }