Research Service, Veterans Affairs Medical Center Denver, CO, USA ; Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver Denver, CO, USA.
Research Service, Veterans Affairs Medical Center Denver, CO, USA ; Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver Denver, CO, USA ; Division of Clinical Pharmacology and Toxicology, Department of Medicine and Neuroscience Program, University of Colorado Denver Aurora, CO, USA.
Front Cell Neurosci. 2014 Oct 7;8:314. doi: 10.3389/fncel.2014.00314. eCollection 2014.
The Rho family of GTPases belongs to the Ras superfamily of low molecular weight (∼21 kDa) guanine nucleotide binding proteins. The most extensively studied members are RhoA, Rac1, and Cdc42. In the last few decades, studies have demonstrated that Rho family GTPases are important regulatory molecules that link surface receptors to the organization of the actin and microtubule cytoskeletons. Indeed, Rho GTPases mediate many diverse critical cellular processes, such as gene transcription, cell-cell adhesion, and cell cycle progression. However, Rho GTPases also play an essential role in regulating neuronal morphology. In particular, Rho GTPases regulate dendritic arborization, spine morphogenesis, growth cone development, and axon guidance. In addition, more recent efforts have underscored an important function for Rho GTPases in regulating neuronal survival and death. Interestingly, Rho GTPases can exert either a pro-survival or pro-death signal in neurons depending upon both the cell type and neurotoxic insult involved. This review summarizes key findings delineating the involvement of Rho GTPases and their effectors in the regulation of neuronal survival and death. Collectively, these results suggest that dysregulation of Rho family GTPases may potentially underscore the etiology of some forms of neurodegenerative disease such as amyotrophic lateral sclerosis.
Rho 家族 GTP 酶属于 Ras 超家族的低分子量（∼21 kDa）鸟嘌呤核苷酸结合蛋白。研究最广泛的成员是 RhoA、Rac1 和 Cdc42。在过去的几十年中，研究表明 Rho 家族 GTP 酶是重要的调节分子，它们将表面受体与肌动蛋白和微管细胞骨架的组织联系起来。实际上，Rho GTP 酶介导许多不同的关键细胞过程，如基因转录、细胞间黏附以及细胞周期进程。然而，Rho GTP 酶在调节神经元形态方面也起着至关重要的作用。特别是，Rho GTP 酶调节树突分支、棘突形态发生、生长锥发育和轴突导向。此外，最近的研究强调了 Rho GTP 酶在调节神经元存活和死亡中的重要功能。有趣的是，Rho GTP 酶可以在神经元中发挥促生存或促死亡信号，具体取决于涉及的细胞类型和神经毒性损伤。这篇综述总结了关键发现，阐述了 Rho GTP 酶及其效应物在调节神经元存活和死亡中的作用。总的来说，这些结果表明 Rho 家族 GTP 酶的失调可能潜在地强调了某些形式的神经退行性疾病（如肌萎缩性侧索硬化症）的病因。
