Li Youjun, Wu Xinzhou, Liu Zhiqiang, Lu Kanghui, Liu Rushi, Guo Xiangrong
Laboratory of Molecular and Cellular Biology, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
Laboratory of Medical Molecular and Immunological Diagnostics, College of Medicine, Hunan Normal University, Changsha 410013, China.
J Cancer. 2020 Jan 1;11(2):345-352. doi: 10.7150/jca.32853. eCollection 2020.
Rac activation is precisely regulated temporally and spatially by intracellular signaling pathways in migrating cells to guarantee the formation of specific cell protrusions-lamellipodia at the leading edge. Integrins-mediated adhesions also control the signaling pathway for localized Rac activation in the cells, but very few studies have been addressed in this field. In the study, we aim to focus on how integrin-mediated signaling affects localized Rac activation by reducing the paxillin expression with shRNA targeting paxillin. The results revealed that reduction of the paxillin expression in the cells inhibited the formation of focal adhesions and Rac activation. By using Rac FRET biosensor, Rac activation was localized at the leading edge of the cell, within the lamellipodium. A ternary complex of paxillin-GIT1-PIX could establish the signaling pathway in front of the cells. Thus, we described a mechanism of integrin-mediated signaling for localized Rac activation that upon ligand binding, activated integrin via the signaling pathway paxillin-GIT1-PIX promotes localized Rac activation at the leading edge and cell migration.
在迁移细胞中，Rac的激活通过细胞内信号通路在时间和空间上受到精确调控，以确保在前沿形成特定的细胞突起——片状伪足。整合素介导的黏附也控制细胞中局部Rac激活的信号通路，但该领域的研究很少。在本研究中，我们旨在通过用靶向桩蛋白的短发夹RNA降低桩蛋白的表达，来关注整合素介导的信号传导如何影响局部Rac激活。结果显示，细胞中桩蛋白表达的降低抑制了黏着斑的形成和Rac的激活。通过使用Rac荧光共振能量转移生物传感器，Rac的激活定位于细胞前沿的片状伪足内。桩蛋白-GIT1-PIX三元复合物可以在细胞前方建立信号通路。因此，我们描述了一种整合素介导的局部Rac激活信号传导机制，即配体结合后，通过桩蛋白-GIT1-PIX信号通路激活整合素，促进前沿局部Rac激活和细胞迁移。
