Faculty of Medicine and Health Technology and BioMediTech, Tampere University, Tampere 33014, Finland.
Fimlab Laboratories, Tampere 33520, Finland.
J Cell Sci. 2019 Apr 3;132(7):jcs226514. doi: 10.1242/jcs.226514.
Talin protein is one of the key components in integrin-mediated adhesion complexes. Talins transmit mechanical forces between β-integrin and actin, and regulate adhesion complex composition and signaling through the force-regulated unfolding of talin rod domain. Using modified talin proteins, we demonstrate that these functions contribute to different cellular processes and can be dissected. The transmission of mechanical forces regulates adhesion complex composition and phosphotyrosine signaling even in the absence of the mechanically regulated talin rod subdomains. However, the presence of the rod subdomains and their mechanical activation are required for the reinforcement of the adhesion complex, cell polarization and migration. Talin rod domain unfolding was also found to be essential for the generation of cellular signaling anisotropy, since both insufficient and excess activity of the rod domain severely inhibited cell polarization. Utilizing proteomics tools, we identified adhesome components that are recruited and activated either in a talin rod-dependent manner or independently of the rod subdomains. This study clarifies the division of roles between the force-regulated unfolding of a talin protein (talin 1) and its function as a physical linker between integrins and the cytoskeleton.
塔林蛋白是整合素介导的黏附复合物的关键组成部分之一。塔林蛋白在β-整合素和肌动蛋白之间传递机械力，并通过力调控的塔林杆域展开调节黏附复合物的组成和信号转导。利用修饰的塔林蛋白，我们证明这些功能参与了不同的细胞过程，可以进行剖析。即使在没有机械调控的塔林杆域亚结构域的情况下，机械力的传递也调节黏附复合物的组成和磷酸酪氨酸信号转导。然而，杆域亚结构域的存在及其机械激活对于黏附复合物的强化、细胞极化和迁移是必需的。塔林杆域的展开对于细胞信号各向异性的产生也是必不可少的，因为杆域的活性不足和活性过高都会严重抑制细胞极化。利用蛋白质组学工具，我们鉴定了黏着斑的组成部分，它们以依赖于塔林蛋白（塔林 1）的机械调控展开的方式或独立于杆域亚结构域的方式被招募和激活。本研究阐明了塔林蛋白的力调控展开与其作为整合素和细胞骨架之间物理连接的功能之间的作用划分。
