PDF(Pubmed)
Abstract：
Talin (herein referring collectively to talin 1 and 2) couples the actomyosin cytoskeleton to integrins and transmits tension to the extracellular matrix. Talin also interacts with numerous additional proteins capable of modulating the actin-integrin linkage and thus downstream mechanosignaling cascades. Here, we demonstrate that the scaffold protein Caskin2 interacts directly with the R8 domain of talin through its C-terminal LD motif. Caskin2 also associates with the WAVE regulatory complex to promote cell migration in an Abi1-dependent manner. Furthermore, we demonstrate that the Caskin2-Abi1 interaction is regulated by growth factor-induced phosphorylation of Caskin2 on serine 878. In MCF7 and UACC893 cells, which contain an amplification of CASKIN2, Caskin2 localizes in plasma membrane-associated plaques and around focal adhesions in cortical microtubule stabilization complexes. Taken together, our results identify Caskin2 as a novel talin-binding protein that might not only connect integrin-mediated adhesion to actin polymerization but could also play a role in crosstalk between integrins and microtubules.
摘要：
Talin将肌动球蛋白细胞骨架与整联蛋白偶联，并将张力传递至细胞外基质。Talin还与许多其他能够调节肌动蛋白-整联蛋白连接的蛋白质相互作用，从而与下游机械信号级联反应。这里,我们证明支架蛋白Caskin2通过其C端LD基序直接与talin的R8结构域相互作用。Caskin2还与WAVE调节复合物结合，以Abi1依赖性方式促进细胞迁移。此外，我们证明Caskin2-Abi1相互作用受生长因子诱导的丝氨酸878上Caskin2磷酸化调节。在MCF7和UACC893细胞中，包含CASKIN2的扩增，Caskin2定位于质膜相关斑块和CMSC的局灶性粘附周围。一起来看,我们的结果确定Caskin2是一种新的talin结合蛋白，它不仅可以连接整合素介导的粘附肌动蛋白聚合，但也可能在整合素和微管之间的串扰中发挥作用。
