Starvation‐induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome–lysosome fusion. (3rd February 2015)

• Record Type: Journal Article
• Authors: Jean, Steve; Cox, Sarah; Nassari, Sonya; Kiger, Amy A
• Is Part Of: EMBO reports. Volume 16:Number 3(2015:Mar.)
• Page Start: 297
• Page End: 311
• Publication Date: 2015-02-03
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201439464
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="main" id="embr201439464-abs-0001"> <title>Abstract</title> <p>Autophagy, the process for recycling cytoplasm in the lysosome, depends on membrane trafficking. We previously identified <italic>Drosophila</italic> Sbf as a Rab21 guanine nucleotide exchange factor (GEF) that acts with Rab21 in endosomal trafficking. Here, we show that Sbf/MTMR13 and Rab21 have conserved functions required for starvation‐induced autophagy. Depletion of Sbf/MTMR13 or Rab21 blocked endolysosomal trafficking of VAMP8, a SNARE required for autophagosome–lysosome fusion. We show that starvation induces Sbf/MTMR13 GEF and RAB21 activity, as well as their induced binding to VAMP8 (or closest <italic>Drosophila</italic> homolog, Vamp7). MTMR13 is required for RAB21 activation, VAMP8 interaction and VAMP8 endolysosomal trafficking, defining a novel GEF‐Rab‐effector pathway. These results identify starvation‐responsive endosomal regulators and trafficking that tunes membrane demands with changing autophagy status.</p> </abstract>