Regulation of Cytoskeletal Crosstalk Controlling Epithelial Cell Adhesion

Abstract

Keratinocytes are specialised epithelial cells in the skin that form the main protective barrier separating the body from the external environment. In order to maintain this intact barrier, keratinocytes must form robust junctions between neighbouring cells as well as with the underlying extracellular matrix (ECM). Cell-cell adhesions are mediated primarily through cadherin receptors, whereas ECM adhesions are provided through the integrin family of transmembrane receptors. However, integrins have been shown to also localise to sites of cell-cell adhesion both in vitro and in vivo, but their role at these sites remains unknown. The aim of this thesis is to analyse the relationship between integrins and the F-actin and MT cytoskeletons in relation to cell-cell and cell-matrix adhesions in keratinocytes, and to identify signalling that regulates cross-talk between adhesion sites. Data demonstrates that α2β1 integrin associated with β-catenin and plays a crucial role in organising both the AJ itself and the associated F-actin and MT networks. Futhermore, α2β1 integrin acts to coordinate the balance between FA and AJ through recruitment of adapter proteins as well as influencing signalling events, particularly the Rho GTPase CDC42.

Date of Award	2017
Original language	English
Awarding Institution	King's College London
Supervisor	Madeline Parsons (Supervisor) & Susan Cox (Supervisor)