Roles of Rho family GTPases in neuronal network formation

神经系统的组织是一个复杂而有条理的过程。这些动态的形态变化。神经元的数量在很大程度上由细胞骨架组织决定。Rho家族GTP酶参与了细胞骨架的调节和随后神经元的形态变化。在众多的Rho家族GTP酶中，Rho诱导轴突收缩，而Rac和CDC42参与轴突生长。然而，其他Rho家族GTP酶的神经功能还没有得到很好的研究。我们研究了RhoG的作用，发现RhoG通过激活PC12细胞中的Rac和CDc42来诱导轴突生长。此外，我们发现Elmo是一种新的RhoG效应因子，并揭示了RhoG的作用机制。通过直接与船坞180相互作用来激活RAC 1，诱导。轴突生长。接下来，我们研究了RND亚家族的神经元功能。然后我们发现RND1与轴突引导因子受体Plexin-B1 Sema4D结合，并通过促进PDZ-Rhogef与Plexin-B1的结合而诱导细胞回缩。我们筛选了RND2的结合伙伴，并鉴定了RND2的新效应物Rapostlin。Rapostlin在N端有FCH结构域，在C端有SH3结构域，调节微管和肌动蛋白细胞骨架的重组。Rapostlin诱导突起分支以响应RND2。

The organization of the nervous system is a complex and orchestrated process. These dynamic morphological changes. of neurons are largely decided by the cytoskeletal organization. Rho family GTPases have been implicated in the regulation of the cytoskeleton and subsequent morphological changes in neurons. Among various Rho family GTPases, Rho induces neurite retraction, while Rac and Cdc42 are involved in neurite outgrowth. However, neural functions of other Rho family GTPases have not yet well investigated. We have examined the role of RhoG and found that RhoG induces neurite outgrowth by activating Rac and Cdc42 in PC12 cells. Furthermore, we identified Elmo as a novel effector of RhoG and revealed that RhoG. activates Rac 1 by direct interaction Elmo with Dock 180, inducing. neurite outgrowth. Next, we examined neuronal function of Rnd subfamily. We then found that Rnd1 binds to Plexin-B1, a receptor for axon guidance factor, Sema4D and induces cell retraction by promoting the binding of PDZ-RhoGEF to Plexin-B 1. We have screened the binding partner of Rnd2 and identified Rapostlin, a novel effector of Rnd2. Rapostlin has FCH domain at the N-terminus and SH3 domain at the C-terminus and regulates reorganization of both microtubule and actin cytoskeleton. Rapostlin induces neurite branching in response to Rnd2.