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


Posted: 2021-10-08 19:00:00
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 Expand 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. Item in Clipboard Xuefeng Fei et al. J Extracell Vesicles. 2021 Oct. Show details Display options Display options Format J Extracell Vesicles . 2021 Oct;10(12):e12153. doi: 10.1002/jev2.12153. Authors 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 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. Item in Clipboard CiteDisplay options Display options Format 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. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. References REFERENCES Bucci, C., Thomsen, P., Nicoziani, P., Mccarthy, J., & Van Deurs, Bo. (2000). Rab7: A key to lysosome biogenesis. Molecular Biology of the Cell. 11, 467-480. Castaño, C., Novials, A., & Párrizas, M. (2019). Exosomes and diabetes. Diabetes/Metabolism Research and Reviews. 35, e3107. Colombo, M., Raposo, G., & Théry, C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annual Review of Cell and Developmental Biology. 30, 255-289. Enchev, R. I., Schulman, B. A., & Peter, M. (2015). Protein neddylation: Beyond cullin-RING ligases. Nature Reviews Molecular Cell Biology. 16, 30-44. Ferrari, G., Langen, H., Naito, M., & Pieters, J. (1999). A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Cell. 97, 435-447. Show all 37 references Grant support Show all 8 grants [x] Cite Copy Format: Send To [x]

参考サイト PubMed: exsome



バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
7月 03, 2021 バイオアソシエイツ

エクソソームを用いた血液検査でパーキンソン病と多系統萎縮症の識別に成功

UCLAヘルスの研究者らは、パーキンソン病と多系統萎縮症(MSA)というよく似た2つの運動障害を見分けることができる血液検査を開発した。この検査法は、脳細胞から送り出されて血液中に混入する「 エクソソーム 」と呼ばれる微小な小胞の内容物を分析することで、パーキンソン病を識別するもので、現在は研究用に限定されている。 今回の研究成果は、2021年5月15日付でActa…

ゲスト 583人 と メンバー 6人 がオンラインです