Investigation for the mechanism of synapse formation by regenerated neurons.

研究再生神经元突触形成的机制。

• 批准号: 20890113
• 负责人: HATA Katsuhiko
• 金额: $ 2.11万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (Start-up)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20890113/
• 关键词: 中枢神経; 再生医療; シナプス; 軸索; 再生阻害蛋白質; RGM; 機能回復; 脊髄; 脊髓

Synapse formation of the cortico-spinal axons is enhanced by RGMa inhibition RGMa binding to its receptor neogenin induces RhoA activation, leading to inhibitory/repulsive behavior and collapse of the neuronal growth cone. However, the precise mechanisms that regulate RhoA activation are poorly understood. In this study, we show that Unc5B, a member of the netrin receptor family, interacts with neogenin as a coreceptor for RGMa. Moreover, leukemia-associated guanine nucleotide exchange factor (LARG) associates with Unc5B to transduce the RhoA signal. Focal adhesion kinase (FAK) is involved in RGMa-induced tyrosine phosphorylation of LARG as well as RhoA activation. These findings uncover the molecular basis for inhibition of synapse formation mediated by RGMa.

通过RGMa抑制增强皮质-脊髓轴突的突触形成。RGMa与其受体再生蛋白结合诱导RhoA活化，导致抑制/排斥行为和神经元生长锥的塌陷。然而，调节RhoA激活的确切机制知之甚少。在这项研究中，我们表明，Unc 5 B，netrin受体家族的成员，与再生蛋白作为RGMa的辅助受体相互作用。此外，白血病相关的鸟嘌呤核苷酸交换因子（LARG）与Unc 5 B联合抑制RhoA信号。粘着斑激酶（FAK）参与RGMa诱导的LARG酪氨酸磷酸化以及RhoA活化。这些发现揭示了RGMa介导的突触形成抑制的分子基础。

项目成果

新規軸索再生阻害因子のシグナル伝達機構

新型轴突再生抑制因子的信号转导机制

• 发表时间: 2009
• 作者: 羽田克彦;山下俊英
• 通讯作者: 山下俊英

RGMaの細胞内シグナル伝達機構

RGMa的细胞内信号传导机制

• 发表时间: 2008
• 作者: 羽田克彦;山下俊英
• 通讯作者: 山下俊英