Control of muscle formation by the fusogenic micropeptide myomixer

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Science  06 Apr 2017:
DOI: 10.1126/science.aam9361

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Skeletal muscle formation occurs through fusion of myoblasts to form multi-nucleated myofibers. From a genome-wide 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.

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