Tks5 and Dynamin-2 enhance actin bundle rigidity in invadosomes to promote myoblast fusion
Tks5 and Dynamin-2 enhance actin bundle rigidity in invadosomes to promote myoblast fusion
复制标题
DOI：
10.1083/jcb.201809161
复制
发表时间：
2019-05-01
影响因子：
7.8
通讯作者：
Liu, Ya-Wen
中科院分区：
文献类型：
--
作者：
Chuang, Mei-Chun;Lin, Shan-Shan;Liu, Ya-Wen
骨骼肌的发育需要分化的成肌细胞的细胞-细胞融合以形成肌纤维。肌动蛋白细胞骨架被认为是成肌细胞融合的主要驱动力，然而，肌动蛋白是如何组织指导细胞间融合仍然不清楚。在这里，我们表明，肌动蛋白和动力蛋白-2-丰富的膨胀结构，侵入体，是所需的融合过程中的肌发生。在分化时，成肌细胞通过关键的侵袭体支架蛋白Tks 5的同种型转换获得形成侵袭体的能力。tks 5直接与发动蛋白2相互作用并将其募集到侵袭体，并调节其在肌动蛋白丝周围的组装，以加强发动蛋白-肌动蛋白束和侵袭体的刚度。这些研究结果提供了一个机制框架，在肌发生过程中肌源性融合机器的收购，并揭示了一种新的结构功能TKS 5和发动蛋白-2在组织肌动蛋白丝的侵袭体驱动膜融合。
Skeletal muscle development requires the cell-cell fusion of differentiated myoblasts to form muscle fibers. The actin cytoskeleton is known to be the main driving force for myoblast fusion; however, how actin is organized to direct intercellular fusion remains unclear. Here we show that an actin- and dynamin-2-enriched protrusive structure, the invadosome, is required for the fusion process of myogenesis. Upon differentiation, myoblasts acquire the ability to form invadosomes through isoform switching of a critical invadosome scaffold protein, Tks5. Tks5 directly interacts with and recruits dynamin-2 to the invadosome and regulates its assembly around actin filaments to strengthen the stiffness of dynamin-actin bundles and invadosomes. These findings provide a mechanistic framework for the acquisition of myogenic fusion machinery during myogenesis and reveal a novel structural function for Tks5 and dynamin-2 in organizing actin filaments in the invadosome to drive membrane fusion.