Roles of the actin-regulatory system in neuronal network formation

肌动蛋白调节系统在神经元网络形成中的作用

• 批准号: 15500235
• 负责人: HOSHINO Mikio
• 金额: $ 1.86万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500235/
• 关键词: Cdk5; p27; cofilin; actin; RhoA; neuronal migration; cerebral cortex; microtubules; Cdks; 子宮内エレクトロポレーション; Rac; JNK; MAP1B; Tiam1; STEF; 脳神経; 分子生物学; 神経科学; Rho; 神経回路; GEF; 神経突起

Rho-family GTPases play key roles in regulating cytoskeletal reorganization, contributing to many aspects of nervous system development. Their activities are known to be regulated by guanine nucleotide exchange factors (GEFs), in response to various extracellular cues. We have been investigating several GEFs for Rac1, such as STEP, Tiam1 and P-Rex1. In this project, we have clarified that, in migrating neurons, STEP and Tiam1 activates Rac1-JNK pathway to phosphorylate MAP1B to regulate microtubule dynamics, eventually contributing to cortical neuronal migration. We have also shown that P-Rex1 transmits extra cellular signals, such as neurotrophins and EGF, to activate the Rac1 pathway, contributing to cortical neuronal migration. Furthermore, we have highlighted that Cdk5 phosphorylates and stabilizes p27kip1, which regulates RhoA-cofilin pathway, controlling actin cytoskeleton of processes of migrating neurons, contributing to cortical neuronal migration. These findings provide new insights into molecular machinery of neuronal network formation.

Rho 家族 GTP 酶在调节细胞骨架重组中发挥关键作用，对神经系统发育的许多方面做出贡献。已知它们的活性受到鸟嘌呤核苷酸交换因子（GEF）的调节，以响应各种细胞外信号。我们一直在研究 Rac1 的多个 GEF，例如 STEP、Tiam1 和 P-Rex1。在这个项目中，我们阐明了在神经元迁移过程中，STEP和Tiam1激活Rac1-JNK通路磷酸化MAP1B来调节微管动力学，最终促进皮质神经元迁移。我们还表明，P-Rex1 传递细胞外信号，例如神经营养因子和 EGF，以激活 Rac1 通路，从而促进皮质神经元迁移。此外，我们强调了 Cdk5 磷酸化并稳定 p27kip1，其调节 RhoA-cofilin 通路，控制神经元迁移过程的肌动蛋白细胞骨架，有助于皮质神经元迁移。这些发现为神经元网络形成的分子机制提供了新的见解。

项目成果

PAR6-PAR3 mediates Cdc42 signaling to Rac activation through STEF/Tiam1, RacGEFs.

PAR6-PAR3 通过 STEF/Tiam1、RacGEF 介导 Cdc42 信号传导至 Rac 激活。

• 期刊: Nature Cell Biology (in press)
• 作者: Kawauchi;et. al.;Nishimura et al.
• 通讯作者: Nishimura et al.

Roles of Racl signaling system in neuronal migration

Racl信号系统在神经元迁移中的作用

• 发表时间: 2005
• 作者: Kawauchi;et. al.;Nishimura et al.;Dezawa et al.;Yoshizawa et al.;星野 幹雄;星野 幹雄;星野 幹雄;Mikio Hoshino
• 通讯作者: Mikio Hoshino

PAR-6-PAR-3 mediates Cdc42 signaling to Rac activation through STEF/Tiaml,RacGEFs

PAR-6-PAR-3 通过 STEF/Tiaml、RacGEF 介导 Cdc42 信号传导至 Rac 激活

• 发表时间: 2005
• 期刊: Nature Cell Biology 113
• 作者: Nishimura;et. al.
• 通讯作者: et. al.

Cdk5 phosphorylates and stabilizes p27^<KipJ>, contributing to actin organization and cortical neuronal migration.

Cdk5 磷酸化并稳定 p27^<KipJ>，有助于肌动蛋白组织和皮质神经元迁移。

• 发表时间: 2006
• 期刊: Nature Cell Biology 8
• 作者: Kawauchi;et. al.
• 通讯作者: et. al.

The in vivo roles of STEF/Tiaml,Racl and JNK in cortical neuronal migration

STEF/Tiaml、Racl 和 JNK 在皮质神经元迁移中的体内作用

• 发表时间: 2003
• 期刊: EMBO Journal 22
• 作者: Kawauchi;et. al.
• 通讯作者: et. al.