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Myomerger induces fusion of non-fusogenic cells and is required for myoblast fusion

Malgorzata E. Quinn, Qingnian Goh, Mitsutoshi Kurosaka, Dilani G. Gamage, Michael J. Petrany, Vikram Prasad, Douglas P. Millay
doi: https://doi.org/10.1101/123158
Malgorzata E. Quinn
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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Qingnian Goh
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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Mitsutoshi Kurosaka
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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Dilani G. Gamage
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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Michael J. Petrany
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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Vikram Prasad
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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Douglas P. Millay
1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
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  • For correspondence: douglas.millay@cchmc.org
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Abstract

Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined1. This lack of knowledge has severely limited our ability to reconstitute cell fusion, which is necessary to decipher the biochemical mechanisms driving plasma membrane merger. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion2,3. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here, we demonstrate that Gm7325, named myomerger, induces the fusion of myomaker-expressing fibroblasts. Cell mixing experiments reveal that while myomaker renders cells fusion-competent, myomerger induces fusogenicity. Thus, myomaker and myomerger confer fusogenic activity to normally non-fusogenic cells. Myomerger is skeletal muscle-specific and only expressed during developmental and regenerative myogenesis. Disruption of myomerger in myoblast cell lines through Cas9-mutagenesis generated non-fusogenic myocytes. Genetic deletion of myomerger in mice results in a paucity of muscle fibers demonstrating a requirement for myomerger in normal muscle formation. Myomerger deficient myocytes exhibit an ability to differentiate and harbor organized sarcomeres, however remain mono-nucleated. These data identify myomerger as a fundamental myoblast fusion protein and establishes a system that begins to reconstitute mammalian cell fusion.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 02, 2017.
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Myomerger induces fusion of non-fusogenic cells and is required for myoblast fusion
Malgorzata E. Quinn, Qingnian Goh, Mitsutoshi Kurosaka, Dilani G. Gamage, Michael J. Petrany, Vikram Prasad, Douglas P. Millay
bioRxiv 123158; doi: https://doi.org/10.1101/123158
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Myomerger induces fusion of non-fusogenic cells and is required for myoblast fusion
Malgorzata E. Quinn, Qingnian Goh, Mitsutoshi Kurosaka, Dilani G. Gamage, Michael J. Petrany, Vikram Prasad, Douglas P. Millay
bioRxiv 123158; doi: https://doi.org/10.1101/123158

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