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Study on molecular structures of synapses and epithelial junctions

突触和上皮连接的分子结构研究

基本信息

批准号：
12470023
负责人：
HATA Yutaka
金额：
$ 7.81万
依托单位：
Tokyo Medical & Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

We have investigated the molecular structures of synapses and epithelial junctions. Through this research, we have revealed the following points ;1. Synaptic scaffolding molecule (S-SCAM) binds p-catenin. This interaction mediates the synaptic targeting of S-SCAM. We have propose the model that b-catenin is first localized at synapses by binding to cadherin, and then recruits to synapses S-SCAM, which provides scaffolds for various components.2. Brain-enriched guanylate kinase-interacting protein (BEGAIN) is localized in the nucleus as well as at synapses. The synaptic targeting of BEGAIN is mediated by its C-terminal region, possibly by the interaction with PSD-95 and depends on NMDA receptor activity.3. Membrane-associated guanylate kinase-interacting protein (MAGUIN) is a mammalian homolog of Drosophila Cnk, and binds to PSD-95 and S-SCAM. The synaptic targeting of MAGUIN is mediated by the pleckstrin homology domain and is independent of the interaction with PSD-95 or S-SCAM.4. Epithelial isoform of S-SCAM named MAGI-1/BAP1 is localized on lateral membranes by its C-terminal PDZ domain.5. A novel PDZ protein, PAPIN, binds p0071, a member of catenin family. However, the subcellular localization of PAPIN does not depend on the interaction with p0071. PAPIN is localized not only on lateral membranes but also on apical membranes. PAPIN interacts with ERBIN, which binds ErbB2 receptor, via p0071, and may be implicated in the EGF-mediated signaling pathway.

我们研究了突触和上皮连接的分子结构。通过本研究，我们发现了以下几点；突触支架分子（S-SCAM）结合对连环蛋白。这种相互作用介导了S-SCAM的突触靶向。我们提出了b-catenin首先通过结合cadherin定位于突触，然后募集到突触S-SCAM，为各种成分提供支架的模型。脑富集鸟苷酸激酶相互作用蛋白（BEGAIN）定位于细胞核和突触。BEGAIN的突触靶向作用由其c端区介导，可能与PSD-95相互作用，并依赖于NMDA受体活性。膜相关鸟苷酸激酶相互作用蛋白（MAGUIN）是一种与果蝇Cnk同源的哺乳动物蛋白，可结合PSD-95和S-SCAM。MAGUIN的突触靶向是由pleckstrin同源结构域介导的，与PSD-95或s - scamn的相互作用无关。S-SCAM的上皮异构体MAGI-1/BAP1通过其c端PDZ结构域定位在侧膜上。一种新的PDZ蛋白，PAPIN，结合了catenin家族成员p0071。然而，PAPIN的亚细胞定位并不依赖于与p0071的相互作用。PAPIN不仅局限于侧膜，而且也局限于根尖膜。PAPIN通过p0071与ERBIN相互作用，ERBIN结合ErbB2受体，并可能参与egf介导的信号通路。