title: Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy.
abstract: Autophagy requires diverse membrane sources and involves membrane trafficking of mATG9, the only membrane protein in the ATG family. However, the molecular regulation of mATG9 trafficking for autophagy initiation remains unclear. Here we identified two conserved classic adaptor protein sorting signals within the cytosolic N-terminus of mATG9, which mediate trafficking of mATG9 from the plasma membrane and trans-Golgi network (TGN) via interaction with the AP1/2 complex. Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation. Our findings uncover novel mechanisms of mATG9 trafficking and suggest a coordination of basal and stress-induced autophagy.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Changqian
authors.initials: C
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Ruize
authors.initials: R
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Guangdong Key Laboratory of Age-related Cardiac-cerebral Vascular Disease, Department of Neurology, Institute of Neurology, The Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, Guangdong 524001, China.
authors.forename: Du
authors.initials: D
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China.|State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001343:Autophagy / Q000187:drug effects; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism*; D000071183:Autophagy-Related Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D017124:Conserved Sequence; D004815:Epidermal Growth Factor / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D013217:Starvation / Q000378:metabolism* / Q000473:pathology*; D013312:Stress, Physiological / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C574794:ATG9A protein, human; D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D019061:src-Family Kinases; D000071189:Autophagy-Related Protein-1 Homolog; C484754:ULK1 protein, human