Studies on Rho-and Ca^<2+>-dependent signaling mechanisms regulating neuronal actin cytoskeleton

Rho和Ca^2依赖性信号传导机制调节神经元肌动蛋白细胞骨架的研究

• 批准号: 15300125
• 负责人: BITO Haruhiko
• 金额: $ 10.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15300125/
• 关键词: calcium; actin; Rho; kinase; cerebellar granule neurons; hippocampal pyramidal neuron; calcium; リン酸化; CaMK; actin; ROCK; mDia; 軸索

1.We examined the signaling pathway downstream of Rho that may be involved in regulating axonogenesis in cerebellar granule neurons in primary culture. These were chosen because these neurons have the interesting property of generating two bipolar axons immediately after plating, prior to further development of neurites, thereby greatly facilitating signaling analyses. We elucidated the essential positive role of the SDF-1α/Rho/mDial pathway in controlling the rate of axon elongation. As we previously discovered a negative regulatory role for the Rho/ROCK cascade, our data suggest that appropriate rate of axonogenesis might be tightly controlled by an antagonism between two distinct Rho effectors, ROCK and mDia1.2.We previously described how synaptic activity-induced calcium mobilization in hippocampal pyramidal neurons triggered actin recruitment to the spines. However, the critical molecules linking calcium with local actin reorganization remained unclear. We here examine whether a novel CaMK we identified as CLICK-III/CaMKIγ was potentially able to fill this role. When overexpressed in vitro, CLICK-III/CaMKIγ was found to be sufficient in promoting and facilitating depolarization-induced neuritogenesis in PC-12 cells.

1.我们检查了 Rho 下游的信号通路，该通路可能参与调节原代培养中小脑颗粒神经元的轴突发生，之所以选择这些神经元是因为这些神经元具有在铺板后、在神经突进一步发育之前立即产生两个双极轴突的有趣特性。 ，从而极大地促进了信号分析，正如我们之前发现的，SDF-1α/Rho/mDial 通路在控制轴突伸长率方面的重要积极作用。 Rho/ROCK 级联，我们的数据表明轴突发生的适当速率可能受到两个不同 Rho 效应器 ROCK 和 mDia1.2 之间的拮抗作用的严格控制。我们之前描述了海马锥体神经元中突触活动诱导的钙动员如何触发肌动蛋白募集然而，将钙与局部肌动蛋白重组联系起来的关键分子仍然缺失，我们在这里检查我们是否发现了一种新的 CaMK。 CLICK-III/CaMKIγ 有可能在体外过表达时发挥这一作用，发现 CLICK-III/CaMKIγ 足以促进和促进 PC-12 细胞中去极化诱导的神经突发生。

项目成果

Arakawa et al.: "Control of axon elongation via an SDF-1a / Rho / mDia pathway in cultured cerebellar granule neurons."J.Cell Biol.. 161. 381-391 (2003)

Arakawa 等人：“在培养的小脑颗粒神经元中通过 SDF-1a / Rho / mDia 途径控制轴突伸长。”J.Cell Biol.. 161. 381-391 (2003)

Molecular cloning and characterization of CLICK-III/CaMKIγ, a novel membrane-anchored neuronal CaMK

CLICK-III/CaMKIγ（一种新型膜锚定神经元 CaMK）的分子克隆和表征

• 发表时间: 2003
• 期刊: J.Biol.Chem. 278
• 作者: Takemoto-Kimura et al.

ROCK inhibitors as new pharmaceutical targets for neurogenesis and prevention from neurodegeneration

ROCK 抑制剂作为神经发生和预防神经变性的新药物靶点

• 发表时间: 2004
• 期刊: Progress in Medicine (in Japanese) 208
• 作者: Bito H.

Cat+/CREB/CBP-dependent gene regulation : a shared mechanism critical in long-term synaptic plasticity and neuronal survival.

Cat /CREB/CBP 依赖性基因调控：对长期突触可塑性和神经元存活至关重要的共享机制。

• 发表时间: 2003
• 期刊: Cell Calcium 34
• 作者: Bite H;Takemoto-Kimura S.
• 通讯作者: Takemoto-Kimura S.

Takemoto-Kimura et al.: "Molecular cloning and characterization of CLICK-III /CaMKIγ, a novel membrane-anchored neuronal CaMK"J.Biol.Chem.. 278. 18597-18605 (2003)

Takemoto-Kimura 等人：“CLICK-III /CaMKIγ（一种新型膜锚定神经元 CaMK）的分子克隆和表征”J.Biol.Chem.. 278. 18597-18605 (2003)