细胞外囊泡因携带着细胞的重要信息，因而在细胞间通讯发挥重要作用，但其形成机制复杂，且有异质性。自噬体是主要降解细胞质蛋白的细胞器，但某些蛋白可通过自噬依赖的方式分泌，其分泌机制尚未阐明。我们前期发现：RAB22A GTPase诱导自噬，且形成自噬MVB，该过程不依赖于ULK1和Beclin1复合物，但依赖于下游的ATG蛋白。同时，RAB22A抑制RAB7，其形成的自噬MVB不能与溶酶体融合，从而其中的LC3阳性ILVs分泌到细胞外，我们定义为自噬外泌体。另外，肿瘤中存在多种能增强诱导自噬的RAB22A突变体。本项目拟：①研究RAB22A诱导自噬MVB的机制及其形成方式；②探讨RAB22A如何抑制RAB7活性；③明确自噬外泌体对肿瘤细胞是否具有功能。本项目的完成将鉴定一种新的细胞外囊泡（自噬外泌体），解析其物质转运与分泌的调控机制及其功能，进而更好理解细胞器的生理功能及其在疾病发生中的作用。

Extracellular vesicles play an important role in intercellular communication because they carry important cell information, but their formation mechanism is complex and heterogeneous. Autophagosomes are organelles that degrade cytoplasmic proteins, but some proteins can be secreted in an autophagy-dependent manner, the mechanism of which has not been clarified. We previously found that RAB22A GTPase induces autophagy and forms autophagic MVB, which does not depend on ULK1 and Beclin1 complex, but depends on downstream ATG protein. At the same time, RAB22A inhibited RAB7, and the autophagic MVB formed by RAB22A could not fuse with lysosomes, so LC3-positive ILVs were secreted extracellular, which was defined as autophagoexosomes. In addition, there are several RAB22A mutants that enhance autophagy induction in tumors. This project aims to: ①study the mechanism and formation mode of RAB22A induced autophagy MVB; ②investigate how RAB22A inhibits RAB7 activity; ③determine whether autophagoexosomes have functions on tumor cells. The completion of this project will identify a new extracellular vesicle (autophagoexosome), and analyze the regulatory mechanism and function of its material transport and secretion, so as to better understand the physiological function of organelles and their role in the occurrence of disease.