Regulation of Neuronal polarity by Rho Family GTPases

Rho 家族 GTP 酶对神经元极性的调节

• 批准号: 13480236
• 负责人: KAIBUCHI Kozo
• 金额: $ 11.39万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480236/
• 关键词: Neuron; Rho; Rho-kinase; CRMP-2; Microtubules; Numb; LARG; IQGAP1; microtubules

Neurons have two types of highly polarized cell processes, axons and dendrites, both of which differentiate from common immature neurites. Initial neuronal polarization begins when one immature neurite becomes an axon and the remaining immature neurites then become dendrites. However, the intracellular mechanisms, which direct the processes to become an axon or dendrites, are largely unclear. Rho family GTPases regulate cytoskeletons, cell adhesions, neuronal polarity and cell migration by extra cellular signals. We have previously identified Rho-kinase, as an effector of Rho. Rho-kinase phosphorylates collapsin response mediator protein-2 (CRMP-2). CRMP-2 plays crucial roles in axonal growth and determination of axon-dendrite fate, thereby establishing and maintaining neuronal polarity. However, the molecular mechanisms by which the CRMP-2 or Rho family GTPases regulate neuronal polarity have been unknown. In this project, we have found the following results. We identified tublin, Num … More b and LARG as CRMP- 2-interacting molecules. (1) Functional analysis of CRMP-2 ; CRMP-2 binds to tubulin-heterodimer and regulates microtubule assembly. CRMP-2 is involved in polarized Numb-mediated endocytosis. (2) Effect of Rho family GTPases on neuronal polarity ; Phosphorylated CRMP-2 by Rho-kinase do not bind to tubulin. CRMP-2 negatively regulates the activity of LARG/Rho signal. Moreover, IQGAP1, an effector of Racl and Cdc42, interacts with CLIP-170. CLIP-170 binds to the growing ends of microtubules and plays pivotal roles in orientation. Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization. (3) Whole body functional analysis ; In C.elegans, UNC-33 is CRMP2 homologue and is expressed in neurons. We identified UNC-43 (calcuim-calmodulin dependent kinase II)-UNC-33-interacting molecule. The results obtained here lead us to better understanding how the Rho family GTPases regulate neuronal polarity. Less

神经元具有高度极化的细胞过程，当一个不成熟的轴突变成轴突，而IMAMATURE神经突的thendrites则是指导该过程成为轴突或在很大程度上不清楚的。地窖信号。我们已经找到了以下结果通过Rho-Indie蛋白不结合-2。 Rac1/cdc42特殊的皮质斑点和Clip-170复合物是针对偏振的微管阵列和细胞偏振的（计算 - 钙统蛋白依赖性激酶II） - unc-33 iitacting分子

项目成果

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Fukata M.等人：“钙粘蛋白介导的细胞-细胞粘附中的Rho家族GTP酶”Nature Rev.Mol.Cell Biol..2.887-897(2001)

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Su L., et al.: "AF-6 controls integrin-mediated cell adhesion by regulating Rap 1 activation through the specific recruitment of Rap1GTP and SPA-1"J.Biol.Chem.. (in press). (2003)

Su L. 等人：“AF-6 通过 Rap1GTP 和 SPA-1 的特异性募集来调节 Rap 1 激活，从而控制整合素介导的细胞粘附”J.Biol.Chem..（出版中）。

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Murai Y.等人：“Rho激酶参与高血压血管疾病：高血压的新治疗靶点”FASEB J.. 15. 1062-1064 (2001)