Vici综合症蛋白EPG5在自噬和内吞运输中同时发挥重要作用。自噬是通过形成自噬小体包裹底物运送到溶酶体降解的过程。内吞运输是将胞外物质和胞膜蛋白转入细胞质并在膜细胞器间转运的过程。自噬和内吞运输之间密切相关：一方面内体为自噬小体形成提供膜来源，并帮助自噬小体成熟；另一方面自噬影响内吞运输效率，并且一些自噬基因在内吞运输中发挥功能。自噬和内吞运输的协同调控对于机体发育和健康至关重要，两条通路的异常都会导致多种疾病的发生。EPG5对于维持两条通路的有序运行必不可少。目前对EPG5的功能和机制研究主要集中在自噬方面，而在内吞运输中的作用完全不清楚。本项目中，我们将利用线虫遗传学、细胞生物学、生物化学等手段，研究EPG5在内吞运输中的作用，并阐述EPG5协同调控内吞运输和自噬通路的分子机制。这些研究将加深我们对EPG5在生理和疾病中功能的理解，并为相关代谢疾病的发生发展及治疗提供重要的理论依据。

The Vici syndrome protein EPG5 functions in both the autophagy and endocytic trafficking pathways. Autophagy involves the enclosure of cytoplasmic material in the autophagosome and its subsequent delivery to the lysosome for degradation. Endocytic trafficking internalizes the extracellular materials and membrane proteins on cell surface within endosomes, which are subsequently transported between the membrane organelles in cytosol. Recent studies indicate a complex interplay between autophagy and endocytic trafficking. Endosomes contribute to membrane source for autophagosome formation, and are also involved in autophagosome maturation. Autophagy affects the efficiency of endocytic trafficking and some autophagy genes participate in the regulation of endocytic trafficking. The coordinate regulation of the autophagy and endocytic trafficking pathways are essential for the development and health of organisms. Dysfunction of both pathways causes a series of metabolic diseases. EPG5, depletion of which causes defects in autophagy and endocytic trafficking, couples the two pathways. The function of EPG5 in autophagy has been extensively studied. However, little is known about the function of EPG5 in the endocytic trafficking pathway. In this proposal, we will investigate the role of EPG5 in endocytic trafficking using C. elegans and mammalian cells. The molecular mechanism by which EPG5 coordinately regulates autophagy and endocytic trafficking will be investigated. These studies will help us to understand the physiological function of EPG5 in the autophagy and endocytic trafficking pathways and also provide insights into how dysfunction of EPG5 leads to the development of related metabolic diseases.