Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Cytoskeleton (Hoboken). 2012 Sep;69(9):644-58. doi: 10.1002/cm.21057. Epub 2012 Aug 20.
CdGAP is a Rac1/Cdc42 specific GTPase activating protein (GAP) that localizes to cell-matrix adhesions through an interaction with the adhesion scaffold α-parvin/actopaxin to regulate lamellipodia formation and cell spreading. Herein, we demonstrate, using a combination of siRNA-mediated silencing and overexpression, that cdGAP negatively regulates directed and random migration by controlling adhesion maturation and dynamics through the regulation of both adhesion assembly and disassembly. Interestingly, cdGAP was also localized to adhesions formed in three-dimensional (3D) matrix environments and cdGAP depletion promoted cancer cell migration and invasion through 3D matrices. These findings highlight the importance of GAP proteins in the regulation of Rho family GTPases and the coordination of the cell migration machinery..
CdGAP 是 Rac1/Cdc42 特异性 GTP 酶激活蛋白 (GAP)，通过与黏附支架 α-伴肌动蛋白/actopaxin 相互作用而定位到细胞-基质黏附处，从而调节片状伪足的形成和细胞铺展。在此，我们通过 siRNA 介导的沉默和过表达的组合，证明 cdGAP 通过控制黏附组装和拆卸来调节黏附成熟和动态，从而负调控定向和随机迁移。有趣的是，cdGAP 也定位于三维 (3D) 基质环境中形成的黏附处，cdGAP 耗竭通过 3D 基质促进癌细胞迁移和侵袭。这些发现强调了 GAP 蛋白在 Rho 家族 GTP 酶调节和细胞迁移机制协调中的重要性。
