Heparan Sulfate Proteoglycans and Signalling in Cell Adhesion

Abstract

Studies on cell adhesion to isolated and purified extracellular matrix molecules in vitro clearly show that substratum-bound matrix molecules can influence cytoskeletal architecture, through some form of transmembrane signalling process. Fibronectin is one such matrix molecule, and its biological properties in terms of the induction of cell adhesion are now known to be mediated by several domains of the molecule, including the “cell”-binding domain which binds to integrin receptors of the β ₁ family (reviewed in Hynes, 1990; Ruoslahti, 1988). Fibronectin has, in addition, both an amino-terminal 29-kD and a 31-kD heparin-binding domain, which we showed previously were involved in the organization of spread cells (Woods et al., 1986). Cells not only attach to fibronectin, but also spread and can form specialized adhesion structures, focal adhesions (reviewed in Burridge et al. 1988; Hynes, 1990; Woods & Couchman, 1988; and see Fig. 1). These are highly specialized foci of cell-matrix interaction where concentrations of specific membrane and cytoskeletal components form a continuum from the substrate to which the cells are attached to the internal microfilament system (Woods & Couchman, 1988). These structures are not found in highly motile cells (Couchman & Rees, 1979), and form concomitantly as migratory cells stop moving and start to export endo-genously synthesized extracellular matrix. Thus, fibroblasts in vitro can exhibit either a locomotory phenotype or a stationary phenotype characterized by the ability of the cells to alter their environment. This is of great importance in many disease processes, since loss of anchorage, and changes in matrix deposition are often causative events in various connective tissue diseases.