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

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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.