Dystroglycan in cell motility and adhesion

Abstract

Dystroglycan (DG) is a ubiqitously expressed cellular adhesion protein, linking the actin cytoskeleton to the extracellular matrix. Previous studies have shown DG to be important in maintaining the mechanical integrity of cells, as well as functioning as a scaffold for the convergence of various intracellular signalling molecules. The protein is also crucial in formation of the basal membrane during embryogenesis, as well as in various subsequent developmental processes. Recent work has highlighted a potential role for DG in cell motility; the protein being observed in dynamic actin-rich structures such as filopodia, as well as interacting with another actin-associated protein, ezrin. Given its structural and mechanotransducive properties, our work is aimed at revealing a role for DG in cell motility and the processes that accompany this, particularly with respect to cell-substrate adhesion. Mouse H2k myoblast cells exhibit a velocity of around 1?m/min, and display a preference for fibronectin during adhesion and spreading. In contrast, during differentiation substrate preference switches to laminin. During adhesion, expression of DG is observed to shift between several cellular compartments depending on the substrate provided, and we observe colocalisation with adhesion-related proteins such as vinculin, FAK, and the marker phosphotyrosine. We can detect DG in the residual ventral membrane of cells, and in whole cells we observe discrete patches of DG staining in what appear to be podosomes. In overexpressing cells we see enrichment of DG at distinct membrane patches, accompanied by an increase in filopodia. Funding is provided by the White Rose Consortium.