Narumiya Shuh, Yasuda Shingo
Department of Pharmacology and Horizontal Medical Research Organization, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
Curr Opin Cell Biol. 2006 Apr;18(2):199-205. doi: 10.1016/j.ceb.2006.02.002. Epub 2006 Feb 17.
The Rho GTPases have been thought to influence cell morphogenesis through remodeling of the actin cytoskeleton. Consistently, downstream targets such as the mDia family of formins and the WASP family proteins induce actin nucleation and polymerization, and another set of downstream effectors, the ROCK family protein kinases, are involved in regulation of actomyosin contractility. However, evidence has now accumulated that Rho GTPases also regulate local dynamics of microtubules. The mDia family proteins, for example, function downstream of Rho to stabilize and align microtubules in interphase cells. Concomitantly, the role of Rho GTPases in animal cell division, once thought to be limited to cytokinesis, has now been shown to extend to mitosis. Recent work indicates that they may function during both spindle orientation and chromosome congression. However, their involvement is cell-type-specific, raising arguments for and against a mitotic role for Rho GTPases.
Rho GTP酶被认为通过重塑肌动蛋白细胞骨架来影响细胞形态发生。一致的是,诸如formin的mDia家族和WASP家族蛋白等下游靶点可诱导肌动蛋白成核和聚合,而另一组下游效应物,即ROCK家族蛋白激酶,则参与调节肌动球蛋白的收缩性。然而,现在已有证据表明,Rho GTP酶也可调节微管的局部动力学。例如,mDia家族蛋白在Rho的下游发挥作用,以稳定间期细胞中的微管并使其排列整齐。与此同时,Rho GTP酶在动物细胞分裂中的作用,曾被认为仅限于胞质分裂,现在已证明其作用可扩展至有丝分裂。最近的研究表明,它们可能在纺锤体定向和染色体汇聚过程中发挥作用。然而,它们的参与具有细胞类型特异性,这引发了关于Rho GTP酶在有丝分裂中作用的支持和反对观点。