摘要
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.
原文 | English |
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頁(從 - 到) | 1670-1685 |
頁數 | 16 |
期刊 | Journal of Cell Biology |
卷 | 218 |
發行號 | 5 |
DOIs | |
出版狀態 | Published - 2019 5月 1 |
All Science Journal Classification (ASJC) codes
- 細胞生物學