Atg9是至今已经发现的Atg家族蛋白中唯一的膜蛋白。研究发现Atg9蛋白主要定位于质膜、高尔基和胞内体，在细胞自噬体的起始和形成发挥关键作用，其分子调控机制尚不清楚。我们发现Atg9蛋白的N端有两个非常保守的adaptor protein分选信号，对Atg9的运输和细胞自噬调控具有重要的作用。磷酸化调控对Atg9的运输可能起着关键作用，同时质谱结果分析证明Atg9的N端存在保守的丝氨酸和酪氨酸磷酸化位点，初步结果表明激酶ULK1参与Atg9丝氨酸位点磷酸化调控。本申请主要鉴定Atg9蛋白的酪氨酸激酶和磷酸酶，分析磷酸化调控Atg9运输和细胞自噬的调控机制，以及不同激酶协同调控Atg9运输分子机制，同时探讨不同激酶调控Atg9的磷酸化对细胞命运的选择决定。

Atg9 is the only multispanning membrane protein among Atg family, which is essential for autophagy in yeast and mammals, highly conserved across species, and ubiquitously existed on multiple cellular membrane components such as plasma membrane, trans-Golgi network and endosomes. This protein has been thought to be involved in the supply of lipids for the formation of autophagosome. The most concern in the field of the research was how to regulate Atg9 trafficking and its contribution to autophagy in mammalian cells. We have identified two adaptor protein sorting signals at the N terminal of Atg9 which interacts with both AP1 and AP2 complex to mediate Atg9 trafficking. We also found that ULK1 kinase is able to directly phosphorylate Atg9 for its redistribution and autophagy initiation. We thus aim to identify the kinases and phosphatases targeting to Atg9 and understand how Atg9 phosphorylations are linked with Atg9 trafficking and autophagy initiation. Future studies will need to address the relationship between the different subpopulations of Atg9 and different kinases corporately regulating Atg9 phosphorylation. We also will focus on addressing the relation of ULK1 and other kinases phosphorylated Atg9 against cell death or senescence, and the possible roles in tumor formation in vivo. Our work will provide novel regulatory mechanism of Atg9 trafficking and autophagy initiation.