title: Myomaker is a membrane activator of myoblast fusion and muscle formation.
abstract: Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibres. However, the identity of muscle-specific proteins that directly govern this fusion process in mammals has remained elusive. Here we identify a muscle-specific membrane protein, named myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is downregulated thereafter. Overexpression of myomaker in myoblasts markedly enhances fusion, and genetic disruption of myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibres. Remarkably, forced expression of myomaker in fibroblasts promotes fusion with myoblasts, demonstrating the direct participation of this protein in the fusion process. Pharmacological perturbation of the actin cytoskeleton abolishes the activity of myomaker, consistent with previous studies implicating actin dynamics in myoblast fusion. These findings reveal a long-sought myogenic fusion protein that controls mammalian myoblast fusion and provide new insights into the molecular underpinnings of muscle formation.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Millay
authors.forename: Jason R
authors.initials: JR
authors.lastname: O'Rourke
authors.forename: Lillian B
authors.initials: LB
authors.lastname: Sutherland
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bezprozvannaya
authors.forename: John M
authors.initials: JM
authors.lastname: Shelton
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009124:Muscle Proteins