Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm

Gonen Golani, Evgenia Leikina, Kamran Melikov, Jarred M. Whitlock, Dilani G. Gamage, Gracia Luoma-Overstreet, Douglas P. Millay, Michael M. Kozlov, Leonid V. Chernomordik

Research output: Contribution to journalArticlepeer-review

Abstract

Myomerger is a muscle-specific membrane protein involved in formation of multinucleated muscle cells by mediating the transition from the early hemifusion stage to complete fusion. Here, we considered the physical mechanism of the Myomerger action based on the hypothesis that Myomerger shifts the spontaneous curvature of the outer membrane leaflets to more positive values. We predicted, theoretically, that Myomerger generates the outer leaflet elastic stresses, which propagate into the hemifusion diaphragm and accelerate the fusion pore formation. We showed that Myomerger ectodomain indeed generates positive spontaneous curvature of lipid monolayers. We substantiated the mechanism by experiments on myoblast fusion and influenza hemagglutinin-mediated cell fusion. In both processes, the effects of Myomerger ectodomain were strikingly similar to those of lysophosphatidylcholine known to generate a positive spontaneous curvature of lipid monolayers. The control of post-hemifusion stages by shifting the spontaneous curvature of proximal membrane monolayers may be utilized in diverse fusion processes.

Original languageEnglish
Article number495
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 21 Jan 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

ASJC Scopus subject areas

  • General
  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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