Control of muscle formation by the fusogenic micropeptide myomixer.

Control of muscle formation by the fusogenic micropeptide myomixer.
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DOI:
10.1126/science.aam9361
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发表时间:
2017-04-21
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Olson EN
Olson EN
中科院分区:
其他
文献类型:
--
作者:
Bi P;Ramirez-Martinez A;Li H;Cannavino J;McAnally JR;Shelton JM;Sánchez-Ortiz E;Bassel-Duby R;Olson EN

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骨骼肌的形成是通过成肌细胞融合形成多核肌纤维而发生的。从全基因组成簇的规则间隔短回文重复序列(CRISPR)功能丧失筛选成肌细胞融合和肌生成所需的基因中,我们发现了一种84个氨基酸的肌肉特异性肽,我们称之为Myomixer。Myomixer表达与成肌细胞分化一致,并且对于胚胎发生期间的融合和骨骼肌形成是必需的。Myomixer定位于质膜,促进成肌细胞融合并与Myomaker(一种促融合膜蛋白)结合。Myomixer与Myomaker一起也可诱导成纤维细胞-成纤维细胞融合和成纤维细胞-成肌细胞融合。我们的结论是,Myomixer-Myomaker对控制肌肉发育过程中肌纤维形成的关键步骤。
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.
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