Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.
Exp Cell Res. 2022 Jun 15;415(2):113134. doi: 10.1016/j.yexcr.2022.113134. Epub 2022 Mar 31.
Fusion of plasma membranes is essential for skeletal muscle development, regeneration, exercise-induced adaptations, and results in a cell that contains hundreds to thousands of nuclei within a shared cytoplasm. The differentiation process in myocytes culminates in their fusion to form a new myofiber or fusion to an existing myofiber thereby contributing more synthetic material to the syncytium. The choice for two cells to fuse and become one could be a dangerous event if the two cells are not committed to an allied function. Thus, fusion events are highly regulated with positive and negative factors to fine-tune the process, and requires muscle-specific fusogens (Myomaker and Myomerger) as well as general cellular machinery to achieve the union of membranes. While a unified vertebrate myoblast fusion pathway is not yet established, recent discoveries should make this pursuit attainable. Not only does myocyte fusion impact the normal biology of skeletal muscle, but new evidence indicates dysregulation of the process impacts pathologies of skeletal muscle. Here, I will highlight the molecular players and biochemical mechanisms that drive fusion events in muscle, and discuss how this key myogenic process impacts skeletal muscle diseases.
质膜融合对于骨骼肌的发育、再生、运动引起的适应至关重要，结果是一个细胞在共享的细胞质中包含数百到数千个核。肌细胞的分化过程最终导致它们融合形成新的肌纤维或融合到现有的肌纤维中，从而为合胞体提供更多的合成物质。如果两个细胞不致力于联合功能，那么两个细胞融合成为一个细胞可能是一个危险的事件。因此，融合事件受到正向和负向因子的高度调节，以微调该过程，并且需要肌特异性融合蛋白（Myomaker 和 Myomerger）以及一般的细胞机制来实现膜的融合。虽然尚未建立统一的脊椎动物成肌细胞融合途径，但最近的发现应该可以实现这一目标。肌细胞融合不仅影响骨骼肌的正常生物学，而且新的证据表明该过程的失调会影响骨骼肌疾病的病理。在这里，我将重点介绍驱动肌肉融合事件的分子参与者和生化机制，并讨论这个关键的成肌过程如何影响骨骼肌疾病。
