Volume 27, No 2, Feb 2017
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 27 Issue 2, February 2017: 184-201 | Open Access
ORIGINAL ARTICLES
Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy
Changqian Zhou1, Kaili Ma1, Ruize Gao1, Chenglong Mu1, Linbo Chen1, Qiangqiang Liu1, Qian Luo1, Du Feng3, Yushan Zhu1 and Quan Chen1,2
1State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China
2State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3Guangdong 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
Correspondence: Quan Chen, E-mail: chenq@ioz.ac.cn; Yushan Zhu, E-mail: zhuys@nankai.edu.cn
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.
10.1038/cr.2016.146
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