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Retractosomes: small extracellular vesicles generated from broken-off retraction fibers

Yizheng Wang^1,2 , Shuaixin Gao³ , Yuheng Liu¹ , Dongju Wang¹ , Boqi Liu¹ , Dong Jiang¹ , Catherine C. L. Wong^3,4,5,6,7 , Yang Chen^3,4 , Li Yu^1,*

¹State Key Laboratory of Membrane Biology, Tsinghua UniversityPeking University Joint Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China
²Joint Graduate Program of Peking-Tsinghua, National Institute of Biological Sciences, Tsinghua University, Beijing, China
³Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University, Beijing, China
⁴School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
⁵Peking-Tsinghua Center for Life Sciences, Beijing, China
⁶Peking University First Hospital, Beijing, China
⁷Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
* Correspondence: Li Yu(liyulab@mail.tsinghua.edu.cn)

Dear Editor,

Various cell protrusions are known to generate extracellular vesicles.1 A migratory cell generates retraction fibers (RFs) and migrasomes during migration. After the cell migrates away, large amounts of RFs break off from the cell and are left behind. The fate of RFs after detaching from cells is currently unknown.2 To investigate the fate of RFs, we observed Tspan4-overexpressing L929 cells with live-cell imaging (Supplementary information, Data S1). We found that during migration, RFs are pulled out at the trailing edge of cells, and migrasomes soon form on the tips or branch points of the RFs. At this stage, the Tspan4 signal is evenly distributed along the RFs (Fig. 1a). Eventually, the RFs start to break. In most cases, the sections of RF far away from the cells break first, which is not surprising, as these sections of RF are formed earlier. Interestingly, after the RFs break up, the Tspan4 signal appears as a large number of small puncta along the paths which were occupied by the RFs (Fig. 1a; Supplementary information, Video S1).

https://doi.org/10.1038/s41422-022-00666-2

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