Cloning of rat ARHGAP4/Cl, a RhoGAP family member expressed in the nervous system that colocalizes with the Golgi complex and microtubules
Cloning of rat ARHGAP4/Cl, a RhoGAP family member expressed in the nervous system that colocalizes with the Golgi complex and microtubules
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DOI：
10.1016/s0169-328x(02)00448-5
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发表时间：
2002-10-30
期刊：
影响因子：
--
通讯作者：
Young, WS
中科院分区：
文献类型：
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作者：
Foletta, VC;Brown, FD;Young, WS
Rho GTPase家族的细胞内分子开关通过调节肌动蛋白细胞骨架来控制多种细胞功能。越来越多的证据表明，这些分子在神经系统中起着至关重要的作用，特别是在神经元迁移和极性、轴突和生长锥引导、树突树突和突触形成过程中。然而，在神经系统中调节Rho GTPase活性的分子却鲜为人知。在此，我们克隆了Rho GTPase激活蛋白家族的成员ARHGAP4，并证明了其与抗利尿激素2受体基因的密切联系。在体外，重组ARHGAP4刺激了Rho GTPases的三个成员，Racl、Cdc42和RhoA的GTPase活性。arhgap4mrna在多个组织中均有表达，在发育和成人神经系统中均有明显表达。在蛋白质水平的进一步分析中，ARHGAP4明显局限于神经系统的特定区域。这些包括海马CA3区的透明层，脑干和纹状体腹侧区的神经元纤维，以及小脑颗粒细胞。在细胞下，内源性ARHGAP4表达定位于高尔基复合体，并可重新分布到微管中，例如在有丝分裂期间。此外，在PC12细胞分化神经突的尖端也观察到不同的蛋白表达。总的来说，这些结果表明，ARHGAP4的表达比以前认为的更广泛，但可能在调节神经系统特定细胞区室中的Rho GTPase家族成员方面具有专门的活性。Elsevier Science B.V.出版
The Rho GTPase family of intracellular molecular switches control multiple cellular functions via the regulation of the actin cytoskeleton. Increasing evidence implicates a critical involvement of these molecules in the nervous system, particularly during neuronal migration and polarity, axon and growth cone guidance, dendritic arborization and synaptic formation. However, the molecules regulating Rho GTPase activities in the nervous system are less known. Here, we present the cloning of rat ARHGAP4, a member of the Rho GTPase activating protein family, and also demonstrate its close linkage to the vasopressin 2 receptor gene. In vitro, recombinant ARHGAP4 stimulated the GTPase activity of three members of Rho GTPases, Racl, Cdc42 and RhoA. ARHGAP4 mRNA expression was observed in multiple tissues with marked expression throughout the developing and adult nervous systems. On closer analysis of protein levels, ARHGAP4 was significantly restricted to specific regions in the nervous system. These included the stratum lucidem in the CA3 area of the hippocampus, neuronal fibers in the ventral region of the brainstem and striatum, and in the cerebellar granule cells. Subcellularly, endogenous ARHGAP4 expression localized to the Golgi complex and could redistribute to the microtubules, for example during mitosis. In addition, distinct protein expression was observed in the tips of differentiating neurites of PC12 cells. Collectively, these results demonstrate that ARHGAP4 is more widely expressed than previously thought but potentially possesses specialized activity in regulating members of the Rho GTPase family in specific cellular compartments of the nervous system. Published by Elsevier Science B.V.