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

Author

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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
    University of Cincinnati)

  • 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)

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.

Suggested Citation

  • Gonen Golani & Evgenia Leikina & Kamran Melikov & Jarred M. Whitlock & Dilani G. Gamage & Gracia Luoma-Overstreet & Douglas P. Millay & Michael M. Kozlov & Leonid V. Chernomordik, 2021. "Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20804-x
    DOI: 10.1038/s41467-020-20804-x
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    Cited by:

    1. Jarred M. Whitlock & Evgenia Leikina & Kamran Melikov & Luis Fernandez Castro & Sandy Mattijssen & Richard J. Maraia & Michael T. Collins & Leonid V. Chernomordik, 2023. "Cell surface-bound La protein regulates the cell fusion stage of osteoclastogenesis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Viviane Tran & Sarah Nahlé & Amélie Robert & Inès Desanlis & Ryan Killoran & Sophie Ehresmann & Marie-Pier Thibault & David Barford & Kodi S. Ravichandran & Martin Sauvageau & Matthew J. Smith & Marie, 2022. "Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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