Control of muscle formation by the fusogenic micropeptide myomixer

被引:352
作者
Bi, Pengpeng [1 ,2 ]
Ramirez-Martinez, Andres [1 ,2 ]
Li, Hui [1 ,2 ]
Cannavino, Jessica [1 ,2 ]
McAnally, John R. [1 ,2 ]
Shelton, John M. [3 ]
Sanchez-Ortiz, Efrain [1 ,2 ]
Bassel-Duby, Rhonda [1 ,2 ]
Olson, Eric N. [1 ,2 ]
机构
[1] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA
[2] Univ Texas Southwestern Med Ctr Dallas, Sen Paul D Wellstone Muscular Dystrophy Cooperat, Dallas, TX 75390 USA
[3] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
关键词
MYOBLAST FUSION; SKELETAL-MUSCLE; STEM-CELLS; MYOGENESIS; MECHANISMS; MYOMAKER; LESSONS; GENOME;
D O I
10.1126/science.aam9361
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:323 / 327
页数:5
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