细胞迁移,胚胎发育的一个关键特征,豁免权,血管生成,和肿瘤转移,是基于肌动蛋白动力学和整合素介导的粘附的协调调节。RhoGTPases通过调节基于肌动蛋白的突出结构在细胞前缘(即层状足和丝状足)和收缩结构(即,应力纤维)在其后缘。虽然时空分析表明了RhoGTP酶在细胞运动过程中在迁移前沿的严格调节,关于RhoGTP酶活性的主要调节因子,如GAP,GEF和GDI,在这个过程中发挥作用。在这次审查中,我们关注RhoA的一个主要负调节剂,p190RhoGAP-A及其接近的同种型p190RhoGAP-B,这是有效细胞迁移所必需的。最近的研究,包括我们的,证明了p190RhoGAP-A的定位和活性经历了复杂的调控机制,考虑到对RhoA的严格监管,还有RhoGTPase家族的其他成员,在细胞外围。
Cell migration, a key feature of embryonic development, immunity, angiogenesis, and tumor metastasis, is based on the coordinated regulation of actin dynamics and integrin-mediated adhesion. Rho GTPases play a major role in this phenomenon by regulating the onset and maintenance of actin-based protruding structures at cell leading edges (i.e. lamellipodia and filopodia) and contractile structures (i.e., stress fibers) at their trailing edge. While spatio-temporal analysis demonstrated the tight regulation of Rho GTPases at the migration front during cell locomotion, little is known about how the main regulators of Rho GTPase activity, such as GAPs, GEFs and GDIs, play a role in this process. In this review, we focus on a major negative regulator of RhoA, p190RhoGAP-A and its close isoform p190RhoGAP-B, which are necessary for efficient cell migration. Recent studies, including our, demonstrated that p190RhoGAP-A localization and activity undergo a complex regulatory mechanism, accounting for the tight regulation of RhoA, but also other members of the Rho GTPase family, at the cell periphery.