Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration.
Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration.
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DOI：
10.3389/fncel.2014.00314
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发表时间：
2014
影响因子：
5.3
通讯作者：
Linseman DA
中科院分区：
文献类型：
--
作者：
Stankiewicz TR;Linseman DA
GTP酶的Rho家族属于低分子量（约21 kDa）鸟嘌呤核苷酸结合蛋白的Ras超家族。研究最广泛的成员是RhoA，Rac 1和Cdc 42。在过去的几十年中，研究表明Rho家族GTP酶是连接表面受体与肌动蛋白和微管细胞骨架的组织的重要调节分子。事实上，Rho GTP酶介导许多不同的关键细胞过程，如基因转录、细胞-细胞粘附和细胞周期进程。然而，Rho GTP酶也在调节神经元形态中发挥重要作用。特别是，Rho GTP酶调节树突状分支、棘形态发生、生长锥发育和轴突导向。此外，最近的努力强调了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存活或促死亡信号，这取决于细胞类型和所涉及的神经毒性损伤。本文综述了Rho GTPases及其效应子参与神经元存活和死亡调控的主要研究结果。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侧索硬化症的病因。
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.
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DOI：
10.1016/j.bbadis.2013.10.013
发表时间：
2014-01-01
影响因子：
6.2
作者：
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DOI：
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期刊：
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作者：
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