2. Academic Validation
  3. Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains

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

  • Nat Cell Biol. 2019 Aug;21(8):991-1002. doi: 10.1038/s41556-019-0367-5.
Yuwei Huang 1 2,  Ben Zucker 3,  Shaojin Zhang 1 2,  Sharon Elias 3,  Yun Zhu 4,  Hui Chen 5,  Tianlun Ding 1 2,  Ying Li 1 2,  Yujie Sun 4,  Jizhong Lou 5,  Michael M Kozlov 6,  Li Yu 7 8
Affiliations

Affiliations

  • 1 The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
  • 2 Beijing Frontier Research Center for Biological Structure, Beijing, China.
  • 3 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 4 The State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
  • 5 Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
  • 6 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. michk@tauex.tau.ac.il.
  • 7 The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. liyulab@mail.tsinghua.edu.cn.
  • 8 Beijing Frontier Research Center for Biological Structure, Beijing, China. liyulab@mail.tsinghua.edu.cn.
PMID: 31371828 DOI: 10.1038/s41556-019-0367-5
Abstract

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.

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