Complex functional interaction between integrin receptors and ion channels.

Abstract. Integrin receptors mediate adhesion of the cell to the extracellular matrix and thereby regulate cell motility, proliferation, differentiation and apoptosis. These processes are frequently accompanied by alterations in ion flow. Recent evidence suggests that integrins can regulate ion channels and form macromolecular complexes, thus contributing to the localization of the channel onto the plasma membrane. Reciprocal regulatory interactions between integrins and ion channels are common and are often accompanied by formation of a multiprotein complex, which can be preferentially located in lipid rafts. Integrin activation stimulates tyrosine kinases, which regulate ion channels and downstream responses in parallel. In other cases, the effects are mediated by G proteins. In turn, ion channel activation stimulates cellular responses by mechanisms that include potentiation of FAK and Src. Moreover, ion channels often feed back on integrin activation and/or expression. Conformational coupling might contribute to these effects. It seems that ion channels sometimes transmit their signals through conformational coupling, instead of change in ion fluxes. Finally, the channel protein is not merely a final target, because it often feeds back by controlling integrin activation and/or expression. These findings have important implications for the physiology of normal and neoplastic cells and suggest interesting perspectives for studies of synaptic plasticity.