Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, Ohio 45229, USA.
Nat Commun. 2017 Jun 1;8:15665. doi: 10.1038/ncomms15665.
Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined, which has severely limited our ability to reconstitute cell fusion. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-expressing fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here we show that Gm7325, which we name myomerger, induces the fusion of myomaker-expressing fibroblasts. Thus, myomaker and myomerger together confer fusogenic activity to otherwise non-fusogenic cells. Myomerger is skeletal muscle-specific and genetic deletion in mice results in a paucity of muscle fibres demonstrating its requirement for normal muscle formation. Myomerger deficient myocytes differentiate and harbour organized sarcomeres but are fusion-incompetent. Our findings identify myomerger as a fundamental myoblast fusion protein and establish a system that begins to reconstitute mammalian cell fusion.
尽管细胞融合对于哺乳动物的发育和生理学非常重要，但对于这个过程至关重要的因素仍有待完全定义，这严重限制了我们重新构建细胞融合的能力。肌形成蛋白（Tmem8c）是一种肌肉特异性蛋白，对于成肌细胞融合是必需的。在成纤维细胞中表达肌形成蛋白会驱动它们与成肌细胞融合，但不会与其他表达肌形成蛋白的成纤维细胞融合，这突出表明融合还需要其他成肌细胞衍生的因子。在这里，我们表明 Gm7325（我们称之为肌联蛋白）诱导表达肌形成蛋白的成纤维细胞融合。因此，肌形成蛋白和肌联蛋白一起赋予原本非融合性的细胞融合活性。肌联蛋白是骨骼肌特异性的，在小鼠中的基因缺失导致肌肉纤维数量减少，表明其对于正常肌肉形成是必需的。肌联蛋白缺失的肌细胞分化并具有组织化的肌节，但融合能力不足。我们的发现将肌联蛋白鉴定为基本的成肌细胞融合蛋白，并建立了一个开始重新构建哺乳动物细胞融合的系统。
