Calpain-mediated proteolysis of talin regulates adhesion dynamics
Calpain-mediated proteolysis of talin regulates adhesion dynamics
复制标题
DOI：
10.1038/ncb1175
复制
发表时间：
2004-10-01
影响因子：
21.3
通讯作者：
Huttenlocher, A
中科院分区：
文献类型：
--
作者：
Franco, SJ;Rodgers, MA;Huttenlocher, A
粘附复合物的动态调节是细胞迁移所必需的，因此已成为细胞运动性研究中的关键问题（1）。最近在确定调节粘附分解的一些分子机制方面取得了进展，包括粘附衔接蛋白和酪氨酸激酶的作用（2）。然而，很少有人知道的潜在贡献的蛋白水解机制的调节粘附复合物的动力学。在这里，我们表明，由细胞内钙依赖性蛋白酶钙蛋白酶的塔林蛋白水解是关键的局部粘附拆卸。我们已经在talin中产生了一个单点突变，使其对钙蛋白酶的蛋白水解具有抗性。粘附组装和拆卸率的定量表明，钙蛋白酶介导的塔林蛋白水解是一个限速步骤，在粘附周转。此外，我们表明，拆卸的其他粘附组件，包括桩蛋白，黏着斑蛋白和zyxin，也依赖于钙蛋白酶切割塔林的能力，表明塔林蛋白水解调节粘附营业额的一般作用。总之，这些研究结果确定钙蛋白酶介导的蛋白水解塔林作为一种机制，粘附动力学调节。
Dynamic regulation of adhesion complexes is required for cell migration and has therefore emerged as a key issue in the study of cell motility(1). Recent progress has been made in defining some of the molecular mechanisms by which adhesion disassembly is regulated, including the contributions of adhesion adaptor proteins and tyrosine kinases(2). However, little is known about the potential contribution of proteolytic mechanisms to the regulation of adhesion complex dynamics. Here, we show that proteolysis of talin by the intracellular calcium-dependent protease calpain is critical for focal adhesion disassembly. We have generated a single point mutation in talin that renders it resistant to proteolysis by calpain. Quantification of adhesion assembly and disassembly rates demonstrates that calpain-mediated talin proteolysis is a rate-limiting step during adhesion turnover. Furthermore, we demonstrate that disassembly of other adhesion components, including paxillin, vinculin and zyxin, is also dependent on the ability of calpain to cleave talin, suggesting a general role for talin proteolysis in regulating adhesion turnover. Together, these findings identify calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics are regulated.