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Science. 2017 Apr 21;356(6335):323-327. doi: 10.1126/science.aam9361. Epub 2017 Apr 6.

Control of muscle formation by the fusogenic micropeptide myomixer.

Author information

1
Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4
Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. eric.olson@utsouthwestern.edu.

Abstract

Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84-amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein. Myomixer together with Myomaker can also induce fibroblast-fibroblast fusion and fibroblast-myoblast fusion. We conclude that the Myomixer-Myomaker pair controls the critical step in myofiber formation during muscle development.

PMID:
28386024
PMCID:
PMC5502127
DOI:
10.1126/science.aam9361
[Indexed for MEDLINE]
Free PMC Article

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