Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, Quebec, H3A 2B2, Canada.
Curr Drug Targets. 2011 Jul 1;12(8):1202-15. doi: 10.2174/138945011795906543.
The establishment of neural connectivity implicates tight regulation of the intracellular signaling pathways mediated by axon guidance molecules. The Rho family of small GTPases, in particular Rho, Rac, and Cdc42, are important regulators of the cytoskeleton in neuronal cells acting, downstream of most, if not all, guidance cue receptors. Furthermore, recent studies using in vivo knockout mouse models provide new evidence of the primary role played by Rho GTPase signaling during the development of the nervous system. Here, we review our recent understanding of Rho GTPase signaling in response to classical axon guidance cues in mammalian cells. We also describe how in vivo knockout mouse models have been useful to implicate Rho GTPase signaling during the formation of the nervous system. Finally, we present several lines of evidence showing the involvement of Rho GTPase signaling in the development and progression of neurodegenerative diseases.
神经连接的建立涉及到由轴突导向分子介导的细胞内信号通路的紧密调节。Rho 家族的小 GTP 酶，特别是 Rho、Rac 和 Cdc42，是神经元细胞中细胞骨架的重要调节剂，它们作用于大多数（如果不是全部）导向线索受体的下游。此外，使用体内基因敲除小鼠模型的最新研究为 Rho GTPase 信号在神经系统发育过程中发挥的主要作用提供了新的证据。在这里，我们回顾了我们最近对哺乳动物细胞中经典轴突导向线索的 Rho GTPase 信号的理解。我们还描述了体内基因敲除小鼠模型如何在神经系统形成过程中有助于暗示 Rho GTPase 信号。最后，我们提出了一些证据表明 Rho GTPase 信号参与了神经退行性疾病的发展和进展。
