Myomaker is a membrane activator of myoblast fusion and muscle formation

Douglas P. Millay, Jason R. O'Rourke, Lillian B. Sutherland, Svetlana Bezprozvannaya, John M. Shelton, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

157 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalNature
Volume499
Issue number7458
DOIs
StatePublished - 2013

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Myoblasts
Muscles
Membranes
Muscle Proteins
Actin Cytoskeleton
Actins
Cause of Death
Mammals
Membrane Proteins
Proteins
Down-Regulation
Fibroblasts
Pharmacology

ASJC Scopus subject areas

  • General

Cite this

Millay, D. P., O'Rourke, J. R., Sutherland, L. B., Bezprozvannaya, S., Shelton, J. M., Bassel-Duby, R., & Olson, E. N. (2013). Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature, 499(7458), 301-305. https://doi.org/10.1038/nature12343

Myomaker is a membrane activator of myoblast fusion and muscle formation. / Millay, Douglas P.; O'Rourke, Jason R.; Sutherland, Lillian B.; Bezprozvannaya, Svetlana; Shelton, John M.; Bassel-Duby, Rhonda; Olson, Eric N.

In: Nature, Vol. 499, No. 7458, 2013, p. 301-305.

Research output: Contribution to journalArticle

Millay, DP, O'Rourke, JR, Sutherland, LB, Bezprozvannaya, S, Shelton, JM, Bassel-Duby, R & Olson, EN 2013, 'Myomaker is a membrane activator of myoblast fusion and muscle formation', Nature, vol. 499, no. 7458, pp. 301-305. https://doi.org/10.1038/nature12343
Millay DP, O'Rourke JR, Sutherland LB, Bezprozvannaya S, Shelton JM, Bassel-Duby R et al. Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature. 2013;499(7458):301-305. https://doi.org/10.1038/nature12343
Millay, Douglas P. ; O'Rourke, Jason R. ; Sutherland, Lillian B. ; Bezprozvannaya, Svetlana ; Shelton, John M. ; Bassel-Duby, Rhonda ; Olson, Eric N. / Myomaker is a membrane activator of myoblast fusion and muscle formation. In: Nature. 2013 ; Vol. 499, No. 7458. pp. 301-305.
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