Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains
- 1 August 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 21 (8), 991-1002
- https://doi.org/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.Keywords
This publication has 32 references indexed in Scilit:
- Migrasomes provide regional cues for organ morphogenesis during zebrafish gastrulationNature, 2019
- Pairing of integrins with ECM proteins determines migrasome formationCell Research, 2017
- The tetraspanin web revisited by super-resolution microscopyScientific Reports, 2015
- Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migrationCell Research, 2014
- The complexity of tetraspaninsBiochemical Society Transactions, 2011
- Lateral organization of membrane proteins: tetraspanins spin their webBiochemical Journal, 2009
- Membrane microdomains and proteomics: Lessons from tetraspanin microdomains and comparison with lipid raftsProteomics, 2006
- Hydrodynamic extrusion of tubes from giant vesiclesEurophysics Letters, 2003
- Tetraspanin Proteins Mediate Cellular Penetration, Invasion, and Fusion Events and Define a Novel Type of Membrane MicrodomainAnnual Review of Cell and Developmental Biology, 2003
- Observations on microextensions from the surface of isolated vertebrate cellsDevelopmental Biology, 1963