Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada V6T 1Z3.
School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
J Cell Sci. 2018 Dec 18;131(24):jcs225144. doi: 10.1242/jcs.225144.
Attachment of cells to the extracellular matrix (ECM) via integrins is essential for animal development and tissue maintenance. The cytoplasmic protein Talin (encoded by in flies) is necessary for linking integrins to the cytoskeleton, and its recruitment is a key step in the assembly of the adhesion complex. However, the mechanisms that regulate Talin recruitment to sites of adhesion are still not well understood. Here, we show that Talin recruitment to, and maintenance at, sites of integrin-mediated adhesion requires a direct interaction between Talin and the GTPase Rap1. A mutation that blocks the direct binding of Talin to Rap1 abolished Talin recruitment to sites of adhesion and the resulting phenotype phenocopies that seen with null alleles of Talin. Moreover, we show that Rap1 activity modulates Talin recruitment to sites of adhesion via its direct binding to Talin. These results identify the direct Talin-Rap1 interaction as a key mechanism for controlling integrin-mediated cell-ECM adhesion.
细胞通过整合素与细胞外基质(ECM)的附着对于动物的发育和组织维持至关重要。细胞质蛋白塔林(在果蝇中由编码)对于将整合素连接到细胞骨架是必需的,并且其募集是黏附复合物组装的关键步骤。然而,调节塔林募集到黏附部位的机制仍未得到很好的理解。在这里,我们表明,塔林募集到整合素介导的黏附部位,并维持在这些部位,需要塔林与 GTPase Rap1 之间的直接相互作用。阻断塔林与 Rap1 直接结合的突变会使塔林无法募集到黏附部位,由此产生的表型与塔林缺失突变体相似。此外,我们还表明,Rap1 活性通过其与塔林的直接结合来调节塔林募集到黏附部位。这些结果确定了塔林 - Rap1 直接相互作用是控制整合素介导的细胞-ECM 黏附的关键机制。