Ishikawa Yukio, Katoh Hironori, Negishi Manabu
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Neurosci Lett. 2006 Jun 12;400(3):218-23. doi: 10.1016/j.neulet.2006.02.064. Epub 2006 Mar 10.
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.
Rho家族小GTP酶是包括树突发生在内的神经元形态发生的关键调节因子。我们最近发现,Rho家族成员Rnd1在突触形成阶段在脑中高度表达,并参与树突棘的形成。然而,Rnd1调节包括棘形态发生在内的树突发育的机制仍不清楚。在这里,我们报告Rho家族成员Rnd1在海马神经元的神经元活动依赖性树突发育中起关键作用。Rnd1的过表达促进了培养的海马神经元的树突生长和分支。另一方面,RNA干扰抑制内源性Rnd1表达显著抑制了神经元活动依赖性树突发育,并且这种抑制作用被RhoA效应器ROCK的抑制所消除。此外,敲低Rnd1也消除了海马神经元中脑源性神经营养因子处理所促进的树突发育。我们的研究结果表明,Rnd1参与了神经元活动依赖性树突发育的信号通路。