Fukata Masaki, Nakagawa Masato, Kaibuchi Kozo
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
Curr Opin Cell Biol. 2003 Oct;15(5):590-7. doi: 10.1016/s0955-0674(03)00097-8.
Polarised cell migration is a tightly regulated process that occurs in tissue development, chemotaxis and wound healing. Rho-family GTPases, including Cdc42, Rac1 and RhoA, play a central role in establishing cell polarisation, which requires asymmetric and ordered distribution of the signalling molecules and the cytoskeleton. Recent advances reveal that Rho GTPases, together with phosphatidylinositol 3-kinase, contribute to asymmetric phosphatidylinositol 3,4,5-trisphosphate distribution via a positive-feedback loop. Phosphatidylinositol 3,4,5-trisphosphate thereby activates the signalling cascades to the cytoskeleton as a second messenger. Rho GTPases also capture and stabilise microtubules through their effectors (e.g. IQGAP1, mDia and Par6) near the cell cortex, leading to polarised cell morphology and directional cell migration. Thus, elucidation of the signal transduction cascades from receptors to Rho GTPases and, subsequently, from Rho GTPases to microtubules has begun.
极化细胞迁移是一个受到严格调控的过程，发生在组织发育、趋化作用和伤口愈合过程中。包括Cdc42、Rac1和RhoA在内的Rho家族小G蛋白在建立细胞极化中起核心作用，这需要信号分子和细胞骨架的不对称且有序分布。最近的进展表明，Rho小G蛋白与磷脂酰肌醇3激酶一起，通过正反馈回路促进磷脂酰肌醇3,4,5-三磷酸的不对称分布。磷脂酰肌醇3,4,5-三磷酸因此作为第二信使激活向细胞骨架的信号级联反应。Rho小G蛋白还通过其效应器（如IQGAP1、mDia和Par6）在细胞皮层附近捕获并稳定微管，导致细胞形态极化和细胞定向迁移。因此，已经开始阐明从受体到Rho小G蛋白，以及随后从Rho小G蛋白到微管的信号转导级联反应。
