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Starvation‐induced MTMR 13 and RAB 21 activity regulates VAMP 8 to promote autophagosome–lysosome fusion
Author(s) -
Jean Steve,
Cox Sarah,
Nassari Sonya,
Kiger Amy A
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439464
Subject(s) - rab , microbiology and biotechnology , lysosome , chemistry , biology , biochemistry , gtpase , enzyme
Autophagy, the process for recycling cytoplasm in the lysosome, depends on membrane trafficking. We previously identified Drosophila Sbf as a Rab21 guanine nucleotide exchange factor ( GEF ) that acts with Rab21 in endosomal trafficking. Here, we show that Sbf/ MTMR 13 and Rab21 have conserved functions required for starvation‐induced autophagy. Depletion of Sbf/ MTMR 13 or Rab21 blocked endolysosomal trafficking of VAMP 8, a SNARE required for autophagosome–lysosome fusion. We show that starvation induces Sbf/ MTMR 13 GEF and RAB 21 activity, as well as their induced binding to VAMP 8 (or closest Drosophila homolog, Vamp7). MTMR 13 is required for RAB 21 activation, VAMP 8 interaction and VAMP 8 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.