Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy.
Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy.
复制标题
基础自噬和饥饿诱导的自噬中 Src 和 ULK1 介导的磷酸化对 mATG9 运输的调节
DOI：
10.1038/cr.2016.146
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发表时间：
2017-02
期刊：
影响因子：
44.1
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Zhou C;Ma K;Gao R;Mu C;Chen L;Liu Q;Luo Q;Feng D;Zhu Y;Chen Q
自噬需要不同的膜来源，并涉及mATG 9的膜运输，mATG 9是ATG家族中唯一的膜蛋白。然而，自噬起始mATG 9运输的分子调控仍不清楚。在这里，我们确定了两个保守的经典衔接蛋白分选信号内的mATG 9的胞质N-末端，介导的运输mATG 9从质膜和trans-Golgi网络（TGN）通过与AP 1/2复合物。Src在Tyr 8处磷酸化mATG 9以维持其在非应激条件下的内吞和组成性运输。响应于饥饿，Src在Tyr 8处和ULK 1在Ser 14处对mATG 9的磷酸化在功能上协同作用以促进mATG 9和AP 1/2复合物之间的相互作用，导致mATG 9从质膜和近核区域重新分布到外周池以启动自噬。我们的研究结果揭示了mATG 9运输的新机制，并提出了基础和应激诱导的自噬的协调。
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.