Cell adhesion machine-associated signaling mechanisms regulating cell behavior

细胞粘附机相关信号机制调节细胞行为

• 批准号: 15002014
• 负责人: TAKEICHI Masatoshi
• 金额: $ 212.99万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15002014/
• 关键词: cadherin; catenin; cell adhesion; synapse; actin; Rho GEF; NMDA receptor; neuron; Cdc42; Tuba; NAWSP; NMDAレセプター; 微小管; Rho; 細胞運動; 細胞骨格; カルシウムポンプ

1) αN-catenin is a cadherin-associated protein. We found that this protein is essential for the stability of synaptic contacts in hippocampal neurons.2) Fat1 is a member of the cadherin superfamily. We showed that this large non-classic cadherin is localized at the basal portions of cell-cell contact, and regulates actin polymerization via its binding to Ena/VASP proteins.3) We identified the role of the Cdc42-specific Rho GEF "Tuba". This enzyme regulates tension of cell-cell junctions, acting upstream of the Cdc42-N-WASP signaling pathway.4) We discovered an unexpected movement of cadherin molecules at cell junctions, which was designated as "cadherin flow". This flow is mediated by retrograde actin flow, which also occurs at cell-cell contact sites.5) We disclosed a novel signaling pathway for gene transcription in hippocampal neurons. Activation of the NMDA receptor resulted in N-terminal truncations of β-catenin, and the cleaved β-catenin was translocated into nuclei This process subsequently activated expression of the Fral gene. We also showed that this gene activation system also occurs in vivo.

1）αN-catenin是一种与钙粘着蛋白相关的蛋白。我们发现该蛋白对于海马神经元中突触接触的稳定性至关重要。2）FAT1是钙粘蛋白超家族的成员。我们表明，这种大型的非经典钙粘蛋白位于细胞 - 细胞接触的基本部分，并通过与ENA/VASP蛋白结合来调节肌动蛋白聚合。3）我们确定了CDC42特异性Rho gef“ tuba”的作用。这种酶调节细胞 - 细胞连接的张力，作用于Cdc42-N-WASP信号通路的上游。4）我们在细胞连接处发现了钙粘蛋白分子的意外运动，该分子被指定为“钙粘蛋白流”。该流程是由逆行肌动蛋白流动介导的，也发生在细胞 - 细胞接触位点。5）我们披露了海马神经元中基因转录的新型信号传导途径。 NMDA受体的激活导致β-catenin的N末端截断，并将裂解的β-catenin转移到核中，此过程随后激活了弗拉尔基因的表达。我们还表明，该基因激活系统也发生在体内。

项目成果

Tanabe, K., Takeichi, M., Nakagawa, S.: "Identification of a nonchordate-type classic cadherin in vertebrates : Chicken Hz cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-secific domain complex."Dev.Dynamics. (in

Tanabe, K.、Takeichi, M.、Nakakawa, S.：“脊椎动物中非脊索动物型经典钙粘蛋白的鉴定：鸡 Hz 钙粘蛋白在神经视网膜的水平细胞中表达，并包含非脊索动物特异性结构域复合物。”Dev

N-catenin deficiency causes defects in axon migration and nuclear organization in restricted regions of the mouse brain.

N-连环蛋白缺乏会导致小鼠大脑受限区域的轴突迁移和核组织缺陷。

• 发表时间: 2006
• 期刊: Dev. Dynamics 235
• 作者: Uemura;M.;Takeichi;M
• 通讯作者: M

Nakagawa, S., Takada, S., Takada, R., Takeichi, M.: "Identification of the laminar-inducing factor : Wnt-signal from the anterior rim induces correct laminar formation of the neural retina in vitro."Develop.Biol.. 260. 414-425 (2003)

Nakakawa, S.、Takada, S.、Takada, R.、Takeichi, M.：“层状诱导因子的鉴定：来自前缘的 Wnt 信号在体外诱导神经视网膜的正确层状形成。”开发。

Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.

• DOI: 10.1083/jcb.200605012
• 发表时间: 2006-10-09
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Otani, Tetsuhisa;Ichii, Tetsuo;Aono, Shinya;Takeichi, Masatoshi
• 通讯作者: Takeichi, Masatoshi

Comichon-like Protein (CNIL) Facilitates Seaetion of HB-EGF and Regulates Proper Development of Cranial Naves.

Comichon 样蛋白 (CNIL) 促进 HB-EGF 的分解并调节颅骨的正常发育。

• 发表时间: 2007
• 期刊: Mol Biol. Cell. 18
• 作者: Hoshino;H;Uchida;T.;Otsuki T.;Kawamoto;S.;Okubo;K;Takeichi;M.;Chisaka;O.
• 通讯作者: O.