Modulation of the integrin-mediated cell adhesion by complex gangliosides

The partecipation of complex gangliosides in the adhesion process was suggested initially by the knoledge that these cell surface components can recognize several bioactive factors in the extracellular environment, including fibronectin. Therefore, early studies tested the possibility that complex gangliosides functioned as receptors for fibronectin. However, a receptorial role of gangliosides fibronectin was never demonstrated convincingly. Moreover, the identification of integrin cell surface glycoprotein receptors for Matrix adhesive proteins - cast in doubt any role for gangliosides in cell adhesion. Subsequently, it was observed that the molecular assembly of adhesion sites - i.e. those structures which mediate the adhesion of cells to tissue culture substrata -implied the preferential distribution of complex gangliosides. Moreover, complex gangliosides were found to colocalize with integrin receptors in adhesion sites. These observations renewed interest in the involvement of complex gangliosides in cell adhesion, pointing to an interaction of complex gangliosides with other components of adhesion sites, such as integrins. Indeed, gangliosides were shown to affect integrin function by modulating the affinity of integrin recptors for their ligands in the extracellular Matrix (fibronectin and vitronectin). Furthermore, the modulation of integrin function by gangliosides was demonstrated to influence the differentiation of neural cells. Thus, complex gangliosides may represent membrane-associated regulators of integrin functions.