Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development.
Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development.
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DOI：
10.1038/ncomms15665
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发表时间：
2017-06-01
影响因子：
16.6
通讯作者：
Millay DP
中科院分区：
文献类型：
--
作者：
Quinn ME;Goh Q;Kurosaka M;Gamage DG;Petrany MJ;Prasad V;Millay DP
尽管细胞融合对于哺乳动物的发育和生理学很重要，但该过程的关键因素仍有待完全确定，这严重限制了我们重建细胞融合的能力。 Myomaker (Tmem8c) 是成肌细胞融合所需的肌肉特异性蛋白。成纤维细胞中肌细胞标记物的表达驱动其与成肌细胞融合，但不与其他表达肌细胞标记物的成纤维细胞融合，这凸显了融合需要额外的成肌细胞衍生因子。在这里，我们发现 Gm7325（我们将其命名为 myomerger）可诱导表达 myomaker 的成纤维细胞的融合。因此，myomaker 和 myomerger 共同赋予非融合细胞融合活性。 Myomerger 是骨骼肌特异性的，小鼠中的基因缺失导致肌肉纤维缺乏，这证明了其对正常肌肉形成的需求。 Myomerger 缺陷的肌细胞可以分化并含有有组织的肌节，但无法融合。我们的研究结果将 myomerger 确定为一种基本的成肌细胞融合蛋白，并建立了一个开始重建哺乳动物细胞融合的系统。细胞融合是骨骼肌发育的基础。作者在此表明，myomerger 在成肌细胞中表达，对于小鼠成肌细胞融合至关重要，并且与 myomaker 合作赋予非融合细胞融合能力。
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. Cellular fusion is fundamental for skeletal muscle development. Here the authors show that myomerger is expressed in myoblasts, is essential for myoblast fusion in mice, and in co-operation with myomaker confers fusogenic ability to non-fusogenic cells.