Nobes C D, Hall A
MRC Laboratory for Molecular Cell Biology, CRC Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, United Kingdom.
J Cell Biol. 1999 Mar 22;144(6):1235-44. doi: 10.1083/jcb.144.6.1235.
Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.
细胞运动在胚胎发育过程中对于建立组织模式和驱动形态发生途径至关重要，在成体中对于组织修复以及引导细胞到达感染部位也很关键。动物细胞通过爬行移动，驱动力主要来自肌动蛋白丝的协同组装和拆卸。小GTP酶Rho、Rac和Cdc42调节肌动蛋白丝的组织，我们已经在体外伤口愈合试验中分析了它们对原代胚胎成纤维细胞运动的贡献。Rac对于片状伪足的突出和向前移动至关重要。Cdc42是维持细胞极性所必需的，这包括将片状伪足活动定位到前沿以及使高尔基体在运动方向上重新定向。Rho在运动过程中是维持细胞黏附所必需的，但应力纤维和黏着斑并非必需。最后，Ras调节黏着斑和应力纤维的周转，这对细胞运动至关重要。我们得出结论，由四种小GTP酶Rho、Rac、Cdc42和Ras控制的信号转导途径协同作用以促进细胞运动。
