Deciphering mechanisms of myoblast fusion

项目总结/摘要 尽管成肌细胞融合对正常肌肉发育和生理学的重要性， 在成肌细胞融合反应过程中直接作用于重塑细胞膜的分子。 阐明融合机制对于充分理解肌肉发育和鉴定新的 增加骨骼肌疾病的治疗策略。我们以前发现，myomaker（Mymk） 和Myomerger（Mymx）对于骨骼肌祖细胞的融合是必需的。此外，异位 这两种膜蛋白的表达诱导否则非融合细胞（成纤维细胞）的融合。为 这是第一次用成肌细胞融合原（无论有多少）建立了基于细胞的重建系统 关于这两种蛋白质如何诱导融合存在问题。我们最近发现，myomaker和 肌融合器通过一种独特的细胞机制，通过分裂它们独立的膜， 重塑活动明显影响融合过程。很明显细胞膜重塑 myomaker和myomerger的活性必须受到高度调节，否则它们可能有可能 危及细胞完整性有了这个补充，我们将扩大我们的计划，以确定新的因素， 调节骨骼肌组织的融合。总的来说，这项工作有望开辟一个新的调查领域 进入肌肉的细胞生物学，并积极影响利用融合来改善再生能力的可能性。 药

Project Summary/Abstract Despite the importance of myoblast fusion for normal muscle development and physiology, relatively little is known about the molecules that directly function to remodel membranes during the myoblast fusion reaction. Elucidation of fusion mechanisms is critical to fully understand muscle development and to identify novel therapeutic strategies to augment skeletal muscle disease. We previously discovered that myomaker (Mymk) and myomerger (Mymx) are essential for the fusion of skeletal muscle progenitors. Moreover, ectopic expression of these two membrane proteins induces fusion of otherwise non-fusogenic cells (fibroblasts). For the first time, this establishes a cell-based reconstitution system with myoblast fusogens, however many questions exist as to how these two proteins induce fusion. We have recently found that myomaker and myomerger drive fusion through a unique cellular mechanism, by dividing their independent membrane remodeling activities to distinctly impact the fusion process. It stands to reason that the membrane-remodeling activities of myomaker and myomerger must be highly regulated or they could have the potential to compromise cellular integrity. With this supplement, we will expand our program to identify novel factors that regulate fusion in skeletal muscle tissue. Overall, this work promises to open up a new area of investigation into the cell biology of muscle and positively impact the possibility to harness fusion to improve regenerative medicine.