Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains

Yuwei Huang, Ben Zucker, Shaojin Zhang, Sharon Elias, Yun Zhu, Hui Chen, Tianlun Ding, Ying Li, Yujie Sun, Jizhong Lou, Michael M. Kozlov, Li Yu

Research output: Contribution to journalArticlepeer-review


Migrasomes are recently discovered cellular organelles that form as large vesicle-like structures on retraction fibres of migrating cells. While the process of migrasome formation has been described before, the molecular mechanism underlying migrasome biogenesis remains unclear. Here, we propose that the mechanism of migrasome formation consists of the assembly of tetraspanin- and cholesterol-enriched membrane microdomains into micron-scale macrodomains, which swell into migrasomes. The major finding underlying the mechanism is that tetraspanins and cholesterol are necessary and sufficient for migrasome formation. We demonstrate the necessity of tetraspanins and cholesterol via live-cell experiments, and their sufficiency by generating migrasome-like structures in reconstituted membrane systems. We substantiate the mechanism by a theoretical model proposing that the key factor driving migrasome formation is the elevated membrane stiffness of the tetraspanin- and cholesterol-enriched macrodomains. Finally, the theoretical model was quantitatively validated by experimental demonstration of the membrane-stiffening effect of tetraspanin 4 and cholesterol.

Original languageEnglish
Pages (from-to)991-1002
Number of pages12
JournalNature Cell Biology
Issue number8
StatePublished - 1 Aug 2019

All Science Journal Classification (ASJC) codes

  • Cell Biology


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