骨骼肌纤维的形成取决于成肌细胞的融合,来生成多核肌肉纤维。Eric Olson及其同事识别和定性了一种以前不知道的骨骼肌特有蛋白,即“成肌蛋白”(myomaker),它是它们融合到多核纤维中所需要的。小鼠“成肌蛋白”的遗传删除完全终止成肌细胞的融合,“成肌蛋白”在肌肉细胞中的被迫表达造成过度融合,而在成纤维细胞中的错误表达则使其具有与成肌细胞融合的能力。这些发现为了解肌肉形成的分子机制提供了新见解,同时“成肌蛋白”驱动非肌肉细胞与肌肉细胞融合的能力也为增强肌肉修复提供了一个新策略。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi: 10.1038/nature12343
Myomaker is a membrane activator of myoblast fusion and muscle formation
Douglas P. Millay, Jason R. O’Rourke, Lillian B. Sutherland, Svetlana Bezprozvannaya, John M. Shelton, Rhonda Bassel-Duby & Eric N. Olson
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.