期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 10, 期 12, 页码 -出版社
WILEY
DOI: 10.1002/jev2.12153
关键词
Coro1a; extracellular vesicles; multivesicular bodies; neddylation; Rab7
类别
资金
- National Key R&D Program of China [2016YFA0501800]
- National Natural Science Foundation of China [82130053, 31970845, 31770951, 31870876, 82001662]
- Major Project of Hangzhou Health Science and Technology Plan [Z20200134]
- Joint Preresearch Fund for Clinical Scientific Research of Hangzhou First People's Hospital Affiliated to Zhejiang University [YYJJ2019Z07]
The study reveals that Coro1a undergoes neddylation modification at K233 by TRIM4, facilitating the recruitment and activation of Rab7. Neddylated Coro1a reduces EV secretion and promotes the production of tumor EVs, making it a potential ideal target for regulating EV biogenesis.
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.
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