Publication Date:
2013-07-23
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739301/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739301/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millay, Douglas P -- O'Rourke, Jason R -- Sutherland, Lillian B -- Bezprozvannaya, Svetlana -- Shelton, John M -- Bassel-Duby, Rhonda -- Olson, Eric N -- F32 AR059484/AR/NIAMS NIH HHS/ -- F32AR05948403/AR/NIAMS NIH HHS/ -- HL-077439/HL/NHLBI NIH HHS/ -- HL-111665/HL/NHLBI NIH HHS/ -- HL093039/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- U01-HL-100401/HL/NHLBI NIH HHS/ -- England -- Nature. 2013 Jul 18;499(7458):301-5. doi: 10.1038/nature12343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23868259" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Fusion
;
Cell Line
;
Membrane Proteins/genetics/metabolism/*physiology
;
Mice
;
Mice, Knockout
;
*Muscle Development
;
Muscle Proteins/genetics/metabolism/*physiology
;
Muscle, Skeletal/cytology/*embryology/metabolism
;
Myoblasts/*cytology/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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