Role of the Rho GTPase-activating protein RICS in neurite outgrowth
Role of the Rho GTPase-activating protein RICS in neurite outgrowth
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DOI：
10.1111/j.1365-2443.2006.00966.x
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发表时间：
2006-06-01
期刊：
影响因子：
2.1
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
--
作者：
Nasu-Nishimura, Yukiko;Hayashi, Tomoatsu;Akiyama, Tetsu
Rho家族的小GTP酶，包括RhoA，Rac 1和Cdc 42，是肌动蛋白细胞骨架的关键调节因子。在神经元系统中，Rho GTP酶激活蛋白（RhoGAPs）及其底物Rho GTP酶参与调节神经元形态发育中的多个过程，包括轴突生长和导向、树突发育和突触形成。RICS主要在脑中表达，在体外作为Cdc 42和Rac 1的RhoGAP蛋白发挥作用。为了研究RICS的生物学功能，我们破坏了小鼠的RICS基因。RICS基因敲除小鼠发育正常，具有生育能力。然而，在体外培养时，Cdc 42活性在RICS-/-神经元高于野生型神经元。与这一发现相一致，来自RICS-/-小鼠的海马和小脑颗粒神经元比野生型小鼠的神经突起更长。这些结果表明，RICS通过调节Cdc 42在体内神经突起延伸中起着重要作用。
The Rho family of small GTPases, including RhoA, Rac1 and Cdc42, are critical regulators of the actin cytoskeleton. In neuronal systems, Rho GTPase-activating proteins (RhoGAPs) and their substrates, Rho GTPases, have been implicated in regulating multiple processes in the morphological development of neurons, including axonal growth and guidance, dendritic elaboration and formation of synapses. RICS is mainly expressed in the brain and functions as a RhoGAP protein for Cdc42 and Rac1 in vitro. To examine the biological function of RICS, we disrupted the RICS gene in mice. RICS knockout mice developed normally and were fertile. However, when cultured in vitro, Cdc42 activity in RICS-/- neurons was higher than that in wild-type neurons. Consistent with this finding, hippocampal and cerebellar granule neurons derived from RICS-/- mice bore longer neurites than those from wild-type mice. These findings suggest that RICS plays an important role in neurite extension by regulating Cdc42 in vivo.