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 () and Leonid V. Chernomordik ()
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Gonen Golani: Sackler Faculty of Medicine
Evgenia Leikina: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Kamran Melikov: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Jarred M. Whitlock: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Dilani G. Gamage: Cincinnati Children’s Hospital Medical Center
Gracia Luoma-Overstreet: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Douglas P. Millay: Cincinnati Children’s Hospital Medical Center
Michael M. Kozlov: Sackler Faculty of Medicine
Leonid V. Chernomordik: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20804-x

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