Small GTPase Rnd1 is involved in neuronal activity-dependent dendritic development in hippocampal neurons
Small GTPase Rnd1 is involved in neuronal activity-dependent dendritic development in hippocampal neurons
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DOI：
10.1016/j.neulet.2006.02.064
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发表时间：
2006-06-12
影响因子：
2.5
通讯作者：
Negishi, Manabu
中科院分区：
文献类型：
--
作者：
Ishikawa, Yukio;Katoh, Hironori;Negishi, Manabu
Rho家族小GTP酶是神经元形态发生包括树突发生的关键调节因子。我们最近的研究表明，Rho家族的成员Rnd1在突触发生阶段在大脑中高度表达，并参与树突棘的形成。然而，Rnd1调节树突发育包括棘形态发生的机制仍然未知。在这里，我们报告Rnd1，Rho家族的成员，在海马神经元的神经元活性依赖性树突发育中起着至关重要的作用。Rnd1的过表达促进培养的海马神经元的树突生长和分支。另一方面，抑制内源性Rnd1表达的RNA干扰显着抑制神经元活性依赖性树突状细胞的发展，这种抑制作用被取消抑制RhoA效应ROCK。此外，敲除Rnd1也取消了海马神经元中脑源性神经营养因子治疗促进的树突发育。我们的研究结果表明，Rnd1参与神经元活性依赖性树突发育的信号通路。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Rho family small GTPases are key regulators for neuronal morphogenesis including dendritogenesis. We recently have shown that Rnd1, a member of the Rho family, is highly expressed in brain during the synaptogenic stage and is involved in dendritic spine formation. However, the mechanism by which Rnd1 regulates dendritic development including spine morphogenesis remains unknown. Here we report that Rnd1, a member of the Rho family, plays a critical role in neuronal activity-dependent dendritic development in hippocampal neurons. Overexpression of Rnd1 promoted dendritic growth and branching in cultured hippocampal neurons. On the other hand, suppression of endogenous Rnd1 expression by RNA interference significantly inhibited neuronal activity-dependent dendritic development and this inhibitory effect was canceled by inhibition of RhoA effector ROCK. In addition, knockdown of Rnd1 also abolished dendritic development promoted by treatment with brain-derived neurotrophic factor in hippocampal neurons. Our findings demonstrate that Rnd1 is involved in signaling pathways of neuronal activity-dependent dendritic development. (c) 2006 Elsevier Ireland Ltd. All rights reserved.