Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila

Carlos I. Ayala, Jung Kim, Thomas P. Neufeld

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The self-degradative process of autophagy is important for energy homeostasis and cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by the target of rapamycin kinase (TOR) under basal conditions, and requires the vesicle trafficking machinery regulated by Rab GTPases. However, the interactions between autophagy, TOR and Rab proteins remain incompletely understood in vivo. Here, we identify Rab6 as a critical regulator of the balance between TOR signaling and autolysosome function. Loss of Rab6 causes an accumulation of enlarged autophagic vesicles resulting in part from a failure to deliver lysosomal hydrolases, rendering autolysosomes with a reduced degradative capacity and impaired turnover. Additionally, Rab6-deficient cells are reduced in size and display defective insulin-TOR signaling as a result of mis-sorting and internalization of the insulin receptor. Our findings suggest that Rab6 acts to maintain the reciprocal regulation between autophagy and TOR activity during distinct nutrient states, thereby balancing autophagosome production and turnover to avoid autophagic stress.

Original languageEnglish (US)
Article numberjcs216127
JournalJournal of cell science
Volume131
Issue number17
DOIs
StatePublished - Sep 1 2018

Bibliographical note

Funding Information:
We would like to thank Drs Anne Ephrusi, Bruce Edgar, David Bilder, Matias Simmons, Julian Dow, Helmut Krämer, Hugo Stocker, Julie Brill, André Dennes and Patrick Dolph for generous gifts of flies and antibodies. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center and the Developmental Studies Hybridoma Bank at the University of Iowa for providing fly stocks and antibodies. This work was supported by National Institutes of Health (grant R01 GM62509) to T.P.N. Deposited in PMC for release after 12 months.

Keywords

  • Autophagy
  • Cathepsin
  • Drosophila
  • Insulin
  • Rab6
  • Target of rapamycin
  • Vesicular trafficking

Fingerprint Dive into the research topics of 'Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila'. Together they form a unique fingerprint.

Cite this