Protein-protein interactions underlying the formation of microdomains on the cell surface

多细胞生物有各种细胞连接和细胞表面称为筏的结构。这些微结构域由一系列独特的蛋白质组成，包括受体、细胞粘附分子、细胞骨架接头蛋白和信号分子。这些成分通过顺序的蛋白质-蛋白质相互作用被组织成一个功能复合物。由于细胞连接和其他微结构域的破坏与各种疾病有关，因此阐明每种蛋白质如何组装成复合物是很重要的。我们研究了一种名为S-SCAM的突触膜相关鸟苷酸激酶（MAGUK）蛋白。我们之前报道过S-SCAM结合β-catenin。在这项研究中，我们已经确定了调节β-catenin降解的Axin作为S-SCAM的结合伙伴。我们还发现S-SCAM诱导了一种名为神经胶质素的细胞粘附分子在突触上的积累，神经胶质素随后将另一种MAGUK蛋白PSD-95招募到突触上。此外，我们还研究了SAPAP（一种与S-SCAM和PSD-95相互作用的细胞骨架接头蛋白）是如何靶向突触的。S-SCAM的一种非神经元亚型被命名为MIAGI-1，它定位于上皮细胞的紧密连接处。我们已经寻找了magi -1相互作用的蛋白，并发现了两个新的分子，JAM4和Carom。JAM4是一种细胞粘附分子，属于免疫球蛋白超家族，参与调节细胞旁通透性。Carom是一种细胞骨架适配蛋白。Carom在体外与MAGI-1结合。然而，在极化上皮细胞中，Carom不集中在紧密连接处，与MAGI-1分离，并与CASK相互作用，CASK也属于MAGUK蛋白家族。这一发现表明蛋白质与蛋白质的相互作用不是稳定的，而是在细胞极性的建立过程中发生变化的。

Multicellular organisms have various cell junctions and the structure termed a raft on the cell surface. These microdomains are composed of unique sets of proteins including receptors, cell adhesion molecules, cytoskeleton adaptor proteins, and signaling molecules. These components are organized as a functional complex through sequential protein-protein interactions. Because the disruption of cell junctions and other microdomains is implicated in various diseases, it is important to clarify how each protein is assembled into the complex.We have studied a synaptic membrane-associated guanylate kinase (MAGUK) protein named S-SCAM. We previously reported that S-SCAM binds β-catenin. In this study, we have identified Axin, which regulates β-catenin degradation, as a binding partner of S-SCAM. We have also found that S-SCAM induces the synaptic accumulation of a cell adhesion molecule named neuroligin, and that neuroligin subsequently recruits another MAGUK protein, PSD-95, to synapses. Moreover, we have studied how SAPAP, a cytoskeleton adaptor protein that interacts with both of S-SCAM and PSD-95, is targeted to synapses.A non-neuronal isoform of S-SCAM is named MIAGI-1 that is localized at tight junctions in epithelial cells. We have searched for MAGI-1-interacting proteins and discovered two novel molecules, JAM4 and Carom. JAM4 is a cell adhesion molecule that belongs to the immunoglobulin superfamily and involved in the regulation of paracellular permeability. Carom is a cytoskeleton adaptor protein. Carom binds to MAGI-1 in vitro. However, in polarized epithelial cells, Carom is not concentrated at tight junctions, is separate from MAGI-1, and interacts with CASK, which also belongs to MAGUK family of proteins. This finding suggests that protein-protein interactions are not stable but change during the establishment of cell polarity.