Investigation of the cross-talk between cell junctions and tetraspanin-enriched microdomains

桥粒是细胞间的连接点，提供细胞间的强粘附。它们将中间细丝连接到细胞间粘附的位置，在承受机械应力的组织中大量存在，如心脏和皮肤。由于遗传或自身免疫性疾病导致的桥粒体粘连失败损害了这些组织的完整性。我们最近的研究表明，四联蛋白CD82可能参与了桥粒粘连的调节。四联蛋白是四种跨膜结构域蛋白，它们在膜上组织相互作用的网络。它们能够相互作用，与其他跨膜蛋白和细胞内信号分子相互作用。tetraspanin CD82能够通过多种机制抑制转移，如抑制迁移和侵袭，促进细胞-细胞粘附。CD82已被证明通过稳定E-cadherin-B-catenin相互作用来促进细胞-细胞粘附。这表明CD82可能在钙粘蛋白介导的细胞粘附中起作用。我们将研究在CD82存在和不存在的情况下上皮细胞的粘附特性，并通过消耗桥粒蛋白和使用生化方法。我们还将使用包括共聚焦显微镜、活细胞成像和超分辨率显微镜在内的多种成像技术，研究CD82存在和不存在时上皮细胞中桥粒蛋白的分布。

Desmosomes are intercellular junctions that provide strong adhesion between cells. They link intermediate filaments to sites of intercellular adhesion and are abundant in tissues that endure mechanical stress, such as the heart and skin. Failure of desmosomal adhesion, as a result of inherited or autoimmune disease compromises the integrity of these tissues. Our recent work suggests that the tetraspanin, CD82 may be involved in the regulation of desmosomal adhesion. Tetraspanins are four transmembrane domain proteins that organise a network of interactions at the membrane. They are able to interact with each other, other transmembrane proteins and intracellular signalling molecules. The tetraspanin CD82 is able to suppress metastasis through multiple mechanisms, such as the inhibition of migration and invasion, and promotion of cell-cell adhesion. CD82 has been shown to promote cell-cell adhesion through the stabilisation of E-cadherin-B-catenin interactions. This suggests that CD82 may play a role in cadherin-mediated cell adhesion. We will investigate the adhesive properties of epithelial cells in the presence and absence of CD82, and through the depletion of desmosomal proteins, and using biochemical approaches. We will also investigate the distribution of desmosomal proteins in epithelial cells in the presence and absence of CD82 using a number of imaging techniques, including confocal microscopy, live cell imaging and super-resolution microscopy.