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Rab35 GTPase recruits NDP52 to autophagy targets
Author(s) -
MinowaNozawa Atsuko,
Nozawa Takashi,
OkamotoFuruta Keiko,
Kohda Haruyasu,
Nakagawa Ichiro
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201796463
Subject(s) - autophagy , biology , mitophagy , microbiology and biotechnology , endosome , ubiquitin , small gtpase , rab , gtpase , phagosome , intracellular , kinase , biochemistry , signal transduction , apoptosis , gene
Autophagy targets intracellular molecules, damaged organelles, and invading pathogens for degradation in lysosomes. Recent studies have identified autophagy receptors that facilitate this process by binding to ubiquitinated targets, including NDP 52. Here, we demonstrate that the small guanosine triphosphatase Rab35 directs NDP 52 to the corresponding targets of multiple forms of autophagy. The active GTP ‐bound form of Rab35 accumulates on bacteria‐containing endosomes, and Rab35 directly binds and recruits NDP 52 to internalized bacteria. Additionally, Rab35 promotes interaction of NDP 52 with ubiquitin. This process is inhibited by TBC 1D10A, a GAP that inactivates Rab35, but stimulated by autophagic activation via TBK 1 kinase, which associates with NDP 52. Rab35, TBC 1D10A, and TBK 1 regulate NDP 52 recruitment to damaged mitochondria and to autophagosomes to promote mitophagy and maturation of autophagosomes, respectively. We propose that Rab35‐ GTP is a critical regulator of autophagy through recruiting autophagy receptor NDP 52.