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Phosphorylation of the exchange factor DENND 3 by ULK in response to starvation activates Rab12 and induces autophagy
Author(s) -
Xu Jie,
Fotouhi Maryam,
McPherson Peter S
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.201440006
Subject(s) - autophagy , guanine nucleotide exchange factor , microbiology and biotechnology , phosphorylation , kinase , chemistry , function (biology) , biology , gtpase , biochemistry , apoptosis
Unc‐51‐like kinases ( ULK s) are the most upstream kinases in the initiation of autophagy, yet the molecular mechanisms underlying their function are poorly understood. We report a new role for ULK in the induction of autophagy. ULK ‐mediated phosphorylation of the guanine nucleotide exchange factor DENND 3 at serines 554 and 572 upregulates its GEF activity toward the small GTP ase Rab12. Through binding to LC 3 and associating with LC 3‐positive autophagosomes, active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK / DENND 3/Rab12 axis in starvation‐induced autophagy.