Department Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Cell Signal. 2011 Jul;23(7):1162-9. doi: 10.1016/j.cellsig.2011.03.001. Epub 2011 Mar 17.
The Integrin-mediated cell adhesion to the extracellular matrix is implicated in the control of proliferation, survival, migration and differentiation of myoblasts. Focal adhesion kinase (FAK) mediates signals from Integrins and plays an essential role in myotube formation. Cdo forms a multiprotein complex that includes other cell adhesion molecules like Cadherins and Boc. Multiple signals emanate from such complexes, including Cdc42 and p38MAPK pathways to activate MyoD. Here we show that C2C12 myoblasts cultured in suspension or on Poly-L-Lysine (PLL), a well known Integrin-independent substratum, failed to express Cdo and MyoD, while the expression of Cadherins and Boc was unchanged. In addition, the activation of Akt and p38MAPK as well as the expression of Cdc42 was affected in these cells. Overexpression of FAK rescued MyoD and Cdo expression as well as myotube formation of C2C12 cells on PLL. Furthermore, reintroduction of Cdo induced enhanced myotube formation on PLL and increased the expression of myogenic markers. Inhibition of ROCK or overexpression of Cdc42-V12 in C2C12 cells upregulated Cdc42 and MyoD expression and rescued defective myoblast differentiation. Taken together, these data indicate that the Integrin/FAK signaling pathway is required for myoblast differentiation by regulating the expression of the promyogenic factors, Cdo, MyoD and Cdc42.
整合素介导的细胞与细胞外基质的黏附参与调控成肌细胞的增殖、存活、迁移和分化。黏着斑激酶（FAK）介导整合素信号，并在肌管形成中发挥重要作用。卷曲蛋白（Cdo）形成一个包含其他细胞黏附分子如钙黏蛋白（Cadherins）和 Boc 的多蛋白复合物。此类复合物发出多种信号，包括 Cdc42 和 p38MAPK 途径以激活 MyoD。我们在此表明，悬浮培养或在聚-L-赖氨酸（PLL，一种已知的非整合素依赖性基质）上培养的 C2C12 成肌细胞未能表达 Cdo 和 MyoD，而 Cadherins 和 Boc 的表达不变。此外，这些细胞中的 Akt 和 p38MAPK 的激活以及 Cdc42 的表达受到影响。FAK 的过表达挽救了 PLL 上 C2C12 细胞的 MyoD 和 Cdo 表达以及肌管形成。此外，Cdo 的再导入诱导 PLL 上增强的肌管形成并增加成肌标志物的表达。抑制 ROCK 或在 C2C12 细胞中过表达 Cdc42-V12 上调 Cdc42 和 MyoD 表达并挽救成肌细胞分化缺陷。总之，这些数据表明整合素/FAK 信号通路通过调节前成肌因子 Cdo、MyoD 和 Cdc42 的表达来调控成肌细胞分化。
