Molecular links between vector transport machinery and cell adhesion machinery

在本项目中，我们分析了载体运输机制和细胞黏附机制之间的分子联系。我们的主要关注点是直接或间接与细胞黏附分子相互作用的膜相关蛋白。我们发现了新的膜相关蛋白，包括Papin、ankycorbin和carom。Papin是一种多PDZ蛋白，可能是一种支架蛋白。Ankycorbin和Carom都与肌动蛋白间接相互作用。有趣的是，Carom在细胞连接成熟之前与MAGI-1相互作用，MAGI-1是一种紧密连接相关蛋白，但在完全极化的上皮细胞中，它与一种不同的膜相关蛋白CASK结合。我们还阐明了膜相关蛋白是如何针对上皮连接的。MAGI-1通过与β-连环蛋白的相互作用被募集到侧膜。Papin和Erbin与连环蛋白家族成员p0071相互作用，但它们的亚细胞定位不依赖于这些相互作用…更多。同样，β-连环蛋白相互作用因子LIN-7被细胞黏附分子Nextin及其相关蛋白afadin招募到侧膜，但不被β-连环蛋白招募。我们还发现了一种与MAGI-1结合的新型细胞黏附分子，并将其命名为JAM4。JAM4和MAGI-1共同调节细胞间通透性。JAM4可能通过激活RAC而增强肝细胞生长因子介导的信号传导。在突触，MAGI-1的神经元亚型S-SCAM被β-连环蛋白招募到基于钙粘连蛋白的黏附部位，随后诱导另一种由神经连接蛋白介导的细胞黏附，并触发肌动蛋白细胞骨架的重塑。类似地，在上皮细胞中，Nectin通过afadin和JAM1的积聚来诱导基于钙粘素的黏附，JAM1是紧密连接的组成部分。此外，我们还发现MAGI-1在肾小球中连接了JAM4和neparin。所有这些发现表明，膜相关蛋白对于连接不同类别的细胞黏附分子是重要的。最后，我们获得了四种与微管结合的新蛋白。较少

In this project, we have analyzed the molecular links between vector transport machinery and cell adhesion machinery. Our primary focus is on membrane-associated proteins that interact directly or indirectly with cell adhesion molecules.We identified novel membrane-associated proteins including PAPIN, ankycorbin, and carom. PAPIN is a multi-PDZ protein and presumably a scaffold protein. Both of ankycorbin and carom indirectly interact with actin. Interestingly, carom interacts with MAGI-1, a tight junction-associated protein, before cell junctions become mature but it comes to bind to CASK, a different membrane-associated protein, in fully polarized epithelial cells. We also clarified how membrane-associated proteins are targeted to epithelial junctions. MAGI-1 is recruited to the lateral membranes through the interaction with beta-catenin. PAPIN and ERBIN interact with p0071, a member of catenin family proteins, but their subcellular localizations are independent of these interactions … More . Likewise, Lin-7, a beta-catenin-interactor, is recruited to the lateral membranes by a cell adhesion molecule, nectin, and its associated protein, afadin, but not by beta-catenin. We also discovered a novel cell adhesion molecule that binds to MAGI-1 and named it JAM4. JAM4 and MAGI-1 co-operate to regulate the intercellular permeability. JAM4 enhances hepatocyte growth factor-mediated signaling putatively by activating Rac. At synapses, a neuronal isoform of MAGI-1 named S-SCAM, which is recruited by beta-catenin to cadherin-based adhesion sites, subsequently induces another cell adhesion mediated by neuroligin and triggers the remodeling of actin cytoskeleton. Similarly, in epithelial cells, nectin induces the cadherin-based adhesion via afadin and the accumulation ofJAM1 that is a component of tight junctions. Moreover, we have found that MAGI-1 links JAM4 and nephrin in kidney glomeruli. All these findings indicate that membrane-associated proteins are important to link different categories of cell adhesion molecules. Finally, we have obtained four novel proteins binding to microtubules. Less