Tom1参与调控自噬过程分子机制的研究

Autophagy is an important intracellular catabolic process involving degradation of harmful cytosolic ingredients by lysosome for the adaptation in response to multiple cellular stresses and the maintenance of cellular homeostasis in eukaryotes. Autophagy process needs many membrane sources, and endosome is one of them. As a member of the ERSCT molecular machine that is crucial for the intracellular endosome transport, Tom1 is reported to directly interact with the motor protein MyosinVI for the maturation of autophagosome. Meanwhile, Tom1 can also directly bind to Tollip, an adaptor protein that plays an important role in the endosome transport process. However, mechanistic bases underlying the specific interactions of Tom1 with MyosinVI and Tollip are still unknown. Based on our previous findings, in this research proposal, we focus on Tom1 and plan to characterize the interactions of Tom1 with MyosinVI and Tollip, thereby to elucidate the molecular mechanism of its role as an adaptor protein in autophagy. So far, good progress has been made in the structural characterization part, and the obtained solid results have laid the foundation for further pursuing the scientific goals in this proposal.

细胞自噬是真核生物通过溶酶体来清除细胞内有害成分以应对内外界细胞压力，维持细胞自身动态平衡的重要代谢途径。自噬途径需要大量膜来源，内涵体是其中重要来源之一。Tom1作为ERSCT家族这一内涵体在细胞内运输的分子机器成员之一，被报道可以通过与肌动蛋白MyosinVI直接作用参与到自噬体的成熟过程，同时Tom1也跟参与内涵体运输过程的受体蛋白Tollip有直接的相互作用，但是目前Tom1结合MyosinVI和Tollip的分子机制未知。基于已有研究成果，本申请课题聚焦Tom1,计划通过研究Tom1与肌动蛋白MyosinVI、受体蛋白Tollip之间的相互作用来阐明其在自噬过程中扮演衔接蛋白的分子机制。目前为止，在结构解析方面已获得很好的研究进展，为申请计划的开展打下了坚实的基础。

细胞自噬是真核生物通过溶酶体来清除细胞内有害成分以应对内外界细胞压力，维持细胞.自身动态平衡的重要代谢途径。自噬途径需要大量膜来源，内涵体是其中重要来源之一。Tom1.作为ERSCT家族这一内涵体在细胞内运输的分子机器成员之一，被报道可以通过与肌动蛋白Myo.sinVI直接作用参与到自噬体的成熟过程，同时Tom1也跟参与内涵体运输过程的受体蛋白Tolli.p有直接的相互作用，但是目前Tom1结合MyosinVI和Tollip的分子机制未知。基于已有研究成.果，本申请课聚焦Tom1,计划通过研究Tom1与肌动蛋白MyosinVI、受体蛋白Tollip之间的相互.作用来阐明其在自噬过程中扮演衔接蛋白的分子机制。目前为止，在结构解析方面已获得很好.的研究进展，为申请计划的开展打下了坚实的基础。