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首页> 外文期刊>The European Journal of Neuroscience >Characterization of the expression of PDZ-RhoGEF, LARG and Galpha12/Galpha13 proteins in the murine nervous system.
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Characterization of the expression of PDZ-RhoGEF, LARG and Galpha12/Galpha13 proteins in the murine nervous system.

机译：鼠神经系统中PDZ-RhoGEF，LARG和Galpha12 / Galpha13蛋白表达的表征。

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摘要

Small GTPases of the Rho-family, like Rho, Rac and Cdc42, are involved in neuronal morphogenesis by regulating growth cone morphology or dendritic spine formation. G-proteins of the G12-family, G12 and G13, couple G-protein-coupled receptors (GPCRs) to the activation of RhoA. Recently, two novel Rho-specific guanine nucleotide exchange factors (RhoGEFs), PDZ-RhoGEF and LARG, have been identified to interact with the activated alpha-subunits of G12/G13 and are thus believed to mediate GPCR-induced Rho activation. Although studies in neuronal cell lines have shown that G12/G13 and PDZ-RhoGEF mediate GPCR-induced neurite retraction, the role, as well as the expression of this signalling pathway, in intact brain has not been adequately studied. In the present study, we have characterized systematically the expression of Galpha12, Galpha13, PDZ-RhoGEF and LARG in various murine tissues as well as their subcellular localization in the central and peripheral nervous systems. By performing immunohistochemistry, using polyclonal antibodies raised against the above proteins, we observed that Galpha12, Galpha13 and their RhoGEF-effectors are distributed widely in the mammalian nervous system. Moreover, these proteins localize to distinct morphological compartments within neurons. While LARG and Galpha12 were mainly found in somata of the neurons, PDZ-RhoGEF and Galpha13 were predominantly localized in the neuropil of central neurons. Interestingly, PDZ-RhoGEF is a neural-specific protein, whereas LARG is nearly ubiqoutous. Our data provide evidence that the G12/13-RhoGEF-mediated pathway is present throughout the adult brain and may be involved in regulation of neuronal morphogenesis and function via GPCRs.
机译：Rho家族的小GTP酶（如Rho，Rac和Cdc42）通过调节生长锥形态或树突棘形成而参与神经元形态发生。 G12家族的G蛋白G12和G13将G蛋白偶联受体（GPCR）偶联到RhoA的激活上。最近，已经确定了两个新颖的Rho特异性鸟嘌呤核苷酸交换因子（RhoGEFs）PDZ-RhoGEF和LARG与G12 / G13的激活的α亚基相互作用，因此被认为可以介导GPCR诱导的Rho激活。尽管对神经元细胞系的研究表明，G12 / G13和PDZ-RhoGEF介导GPCR诱导的神经突退缩，但尚未对完整大脑中的作用以及该信号通路的表达进行充分研究。在本研究中，我们已经系统地表征了各种鼠类组织中Galpha12，Galpha13，PDZ-RhoGEF和LARG的表达以及它们在中枢和周围神经系统中的亚细胞定位。通过进行免疫组织化学，使用针对上述蛋白的多克隆抗体，我们观察到Galpha12，Galpha13及其RhoGEF效应物广泛分布在哺乳动物的神经系统中。而且，这些蛋白质定位于神经元内不同的形态区室。虽然LARG和Galpha12主要存在于神经元的躯体中，但PDZ-RhoGEF和Galpha13主要位于中枢神经元的神经纤维中。有趣的是，PDZ-RhoGEF是一种神经特异性蛋白，而LAR​​G几乎无处不在。我们的数据提供了证据，表明G12 / 13-RhoGEF介导的通路存在于整个成年大脑中，并且可能通过GPCR参与神经元形态发生和功能的调节。

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