Bidaud-Meynard Aurélien, Binamé Fabien, Lagrée Valérie, Moreau Violaine
a Institut National de la Santé et de la Recherche Médicale , Bordeaux , France.
b Université de Bordeaux, Unité Mixte de Recherche 1053 Bordeaux Research In Translational Oncology , Bordeaux , France.
Small GTPases. 2019 Mar;10(2):99-110. doi: 10.1080/21541248.2017.1280584. Epub 2017 Mar 13.
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.
细胞迁移是胚胎发育、免疫、血管生成和肿瘤转移的关键特征，它基于肌动蛋白动力学和整合素介导的黏附的协调调节。Rho GTP酶通过调节细胞前缘基于肌动蛋白的突出结构（即片状伪足和丝状伪足）以及后缘的收缩结构（即应力纤维）的起始和维持，在这一现象中发挥主要作用。虽然时空分析表明在细胞运动过程中Rho GTP酶在迁移前沿受到严格调控，但对于Rho GTP酶活性的主要调节因子，如GAP、GEF和GDI，如何在这一过程中发挥作用却知之甚少。在本综述中，我们重点关注RhoA的主要负调节因子p190RhoGAP-A及其密切异构体p190RhoGAP-B，它们是高效细胞迁移所必需的。包括我们的研究在内的近期研究表明，p190RhoGAP-A的定位和活性经历了复杂的调节机制，这不仅解释了RhoA，也解释了Rho GTP酶家族其他成员在细胞周边的严格调控。
