Phosphorylation of the exchange factor DENND 3 by ULK in response to starvation activates Rab12 and induces autophagy

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.