REAL

Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila

Takáts, Szabolcs and Nagy, Péter and Varga, Ágnes and Pircs, Karolina and Kárpáti, Manuéla and Varga, Kata and Kovács, Attila L and Hegedűs, Krisztina and Juhász, Gábor (2013) Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila. The Journal of cell biology, 201 (4). pp. 531-539. ISSN 1540-8140

[img]
Preview
Text
J Cell Biol-2013-Tak�ts-531-9.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial Share Alike.

Download (3MB) | Preview

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.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
Depositing User: Dr. Gabor Juhasz
Date Deposited: 18 Sep 2014 13:57
Last Modified: 17 May 2018 10:21
URI: http://real.mtak.hu/id/eprint/15361

Actions (login required)

Edit Item Edit Item