Neddylation of Coro1a determines the fate of multivesicular bodies and biogenesis of extracellular vesicles

Journal of Extracellular Vesicles

Yi Sun¹  Yongchao Zhao¹  Zhaoming Ye²  Jing Zhang³  Jianli Wang⁴  Yingying Shen⁵  Xuefeng Fei⁵  Xianghui Kong⁵  Zhijian Cai⁵  Xinliang Lu⁵  Zhijie Li⁵  Jiaoli Wang⁶  Shaofang Xie⁷  Xu Li⁷  Diya Yang⁸ 

[1] Cancer Institute of the Second Affiliated Hospital, and Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou China;Department of Orthopaedics Musculoskeletal Tumour Centre of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China;Department of Pathology of the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China;Institute of Immunology Bone Marrow Transplantation Centre of the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China;Institute of Immunology Department of Orthopaedics of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China;Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine Hangzhou China;School of Life Science Westlake University Hangzhou China;Xinyuan Institute of Medicine and Biotechnology School of Life Sciences Zhejiang Sci‐Tech University Hangzhou China;

关键词: Coro1a;    extracellular vesicles;    multivesicular bodies;    neddylation;    Rab7;   

DOI  :  10.1002/jev2.12153

来源: DOAJ

【 摘 要 】

Abstract Multivesicular bodies (MVBs) fuse with not only the plasma membranes to release extracellular vesicles (EVs) but also lysosomes for degradation. Rab7 participates in the lysosomal targeting of MVBs. However, the proteins on MVB that directly bind Rab7, causing MVB recruitment of Rab7 remain unidentified. Here, we show that Coro1a undergoes neddylation modification at K233 by TRIM4. Neddylated Coro1a is associated with the MVB membrane and facilitates MVB recruitment and activation of Rab7 by directly binding Rab7. Subsequently, MVBs are targeted to lysosomes for degradation in a Rab7‐dependent manner, leading to reduced EV secretion. Furthermore, a decrease in neddylated Coro1a enhances the production of tumour EVs, thereby promoting tumour progression, indicating that neddylated Coro1a is an ideal target for the regulation of EV biogenesis. Altogether, our data identify a novel substrate of neddylation and reveal an unknown mechanism for MVB recruitment of Rab7, thus providing new insight into the regulation of EV biogenesis.

【 授权许可】

Unknown