2. Academic Validation
  3. Neddylation of Coro1a determines the fate of multivesicular bodies and biogenesis of extracellular vesicles

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

  • J Extracell Vesicles. 2021 Oct;10(12):e12153. doi: 10.1002/jev2.12153.
Xuefeng Fei 1,  Zhijie Li 1,  Diya Yang 2,  Xianghui Kong 1,  Xinliang Lu 1,  Yingying Shen 1,  Xu Li 3,  Shaofang Xie 3,  Jiaoli Wang 4 5,  Yongchao Zhao 6,  Yi Sun 6,  Jing Zhang 7,  Zhaoming Ye 8,  Jianli Wang 9 10,  Zhijian Cai 1
Affiliations

Affiliations

  • 1 Institute of Immunology, Department of Orthopaedics of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
  • 3 School of Life Science, Westlake University, Hangzhou, China.
  • 4 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.
  • 5 Zhejiang University Cancer Centre, Hangzhou, China.
  • 6 Cancer Institute of the Second Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 7 Department of Pathology of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 8 Department of Orthopaedics, Musculoskeletal Tumour Centre of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 9 Institute of Immunology, Bone Marrow Transplantation Centre of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 10 Institute of Haematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China.
PMID: 34623756 DOI: 10.1002/jev2.12153
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.

Keywords

Coro1a; Rab7; extracellular vesicles; multivesicular bodies; neddylation.

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