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

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1644024 Studentship BB/M01116X/1 05/10/2015 30/09/2019 Maryam Arab
 
Description The tetraspanin CD82 acts as a scaffolding protein and brings proteins into close proximity for them to interact. This work has shown that the tetraspanin CD82 increase cell-cell adhesion. More specifically, desmosomal and adherens junction mediated adhesion. Desmosomes and adherens junctions are intercellular junctions that provide adhesion between cells. The increase in desmosomal adhesion may come about through interactions of CD82 with another protein called PKCalpha which has previously been shown to modify desmosomal proteins. The increase in adhesion then may result in a change in the organisation of desmosomes. However, the possibility that the change in organisation of desmosomes results in increased adhesion also remains.
Exploitation Route The outcomes of this funding could be used to inform future studies that involve studying the ultrastructure of desmosomes using 3D-STORM.
Sectors Healthcare

 
Description Biochemical Society General Travel Grant
Amount £532 (GBP)
Organisation Biochemical Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2018