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是一种钙粘蛋白相关蛋白。我们发现该蛋白对海马神经元突触接触的稳定性至关重要。2）Fat 1是钙粘蛋白超家族的成员。我们发现这种大的非经典钙粘蛋白定位于细胞-细胞接触的基底部分，并通过其与Ena/VASP蛋白的结合来调节肌动蛋白聚合。3）我们鉴定了Cdc 42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Cdc 42-N-WASP信号通路的上游。4）我们发现了钙粘蛋白分子在细胞连接处的意外运动，这被称为“钙粘蛋白流”。这种流动是由肌动蛋白逆行流动介导的，这种流动也发生在细胞-细胞接触位点。5）我们揭示了海马神经元中基因转录的一种新的信号通路。NMDA受体的激活导致β-catenin的N-末端截短，并且切割的β-catenin易位到细胞核中。该过程随后激活Fral基因的表达。我们还表明，这种基因激活系统也发生在体内。

项目成果

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。

N-cadherin mediates cortical organization in the mouse brain

• DOI: 10.1016/j.ydbio.2006.12.014
• 发表时间: 2007-04-01
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Kadowaki, Masakazu;Nakamura, Shoko;Takeichi, Masatoshi
• 通讯作者: Takeichi, Masatoshi

Tamporal and spatial expression profiles of the Fat3 protein, a giant cadherin molecule, during mouse development.

Fat3 蛋白（一种巨大的钙粘蛋白分子）在小鼠发育过程中的颞叶和空间表达谱。

• 发表时间: 2006
• 期刊: Develop. Dynamics 236
• 作者: Nagae;S.;Tanoue;T.;Takeichi;M.
• 通讯作者: M.

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