Study on molecular structures of synapses and epithelial junctions

我们研究了突触和上皮性连接的分子结构。通过本研究，我们揭示了以下几点：1.突触支架分子(S-SCAM)与p-连环素结合。这种相互作用介导了S-SCAM的突触靶向。我们提出了b-catenin首先通过与钙粘附素结合定位于突触，然后招募到为各种成分提供支架的突触S-SCAM的模型。脑富集型鸟苷酸激酶相互作用蛋白(Begain)定位于细胞核和突触。Begain的突触靶向性是由其C末端区域介导的，可能是通过与PSD-95的相互作用，并依赖于NMDA受体的活性。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，与PSD-95和S-SCAM结合。MAGUIN的突触靶向性是由Pleckstrin同源结构域介导的，不依赖于与PSD-95或S-SCAM的相互作用。S-SCAM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与连环蛋白家族成员p0071结合。然而，Papin的亚细胞定位不依赖于与p0071的相互作用。Papin不仅定位于侧膜，也定位于顶膜。Papin通过p0071与Erbin相互作用，Erbin与ErbB2受体结合，可能参与了EGF介导的信号通路。

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.