Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.

Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.
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DOI:
10.1155/2015/632450
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发表时间:
2015
影响因子:
--
通讯作者:
Shi L
Shi L
中科院分区:
生物学3区
文献类型:
--
作者:
Bai Y;Xiang X;Liang C;Shi L

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Rho家族GTP酶,包括RhoA、Rac1和Cdc42作为研究最多的成员,是肌动蛋白细胞骨架组织的主要调节者。Rho GTP酶控制神经系统的各个方面,并且与许多神经精神疾病和神经退行性疾病相关。Rho GTP酶的活性受两个调节因子家族的控制,作为激活剂的鸟嘌呤核苷酸交换因子(GEF)和作为抑制剂的GTP酶激活蛋白(GAP)。通过GEF和GAP的协调调节,Rho GTP酶作为会聚信号分子在神经系统中传递不同的上游信号。到目前为止,已经在哺乳动物中鉴定了70多个Rho GTP酶的GEF或GAP成员,但其中只有一小部分具有众所周知的功能。因此,重要的GEF和GAP在神经系统中的表征是至关重要的时空动力学的Rho GTdR活性在不同的神经元功能的理解。在这篇综述中,我们总结了目前对Rac1的GEF和GAP的理解,重点是这些调节剂在神经系统中的分子功能和疾病意义。
Rho family GTPases, including RhoA, Rac1, and Cdc42 as the most studied members, are master regulators of actin cytoskeletal organization. Rho GTPases control various aspects of the nervous system and are associated with a number of neuropsychiatric and neurodegenerative diseases. The activity of Rho GTPases is controlled by two families of regulators, guanine nucleotide exchange factors (GEFs) as the activators and GTPase-activating proteins (GAPs) as the inhibitors. Through coordinated regulation by GEFs and GAPs, Rho GTPases act as converging signaling molecules that convey different upstream signals in the nervous system. So far, more than 70 members of either GEFs or GAPs of Rho GTPases have been identified in mammals, but only a small subset of them have well-known functions. Thus, characterization of important GEFs and GAPs in the nervous system is crucial for the understanding of spatiotemporal dynamics of Rho GTPase activity in different neuronal functions. In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system.
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