Recent insights into ligand binding, activation and signalling by integrin adhesion receptors

In recent years, analyses of the structure and function of membrane-intercalated adhesion molecules have shown them to play key roles in determining cellular phenotype. As expected, adhesion has an important role in regulating cellular positioning, but there is also compelling evidence that information transduced via adhesion molecules affects the differentiation status of cells. Cell surface adhesion molecules can be classified into a number of gene families, including immunoglobulins, cadherins, selectins, proteoglycans, and integrins. All of these types of molecule are co-expressed on most cells, and therefore the overall contribution of adhesion to cell phenotype is likely to be a net effect of the individual contributions of each of these groups. In this review, we will focus on the role of the integrins, which appear to be particularly important mediators of cell migration and adhesion-dependent intracellular signalling. A great deal is now known about the extracellular faces of integrins, including their structure and ligand-binding mechanisms, and in recent years, our knowledge of integrin-dependent signalling via cytoplasmic domains has improved considerably. An emerging picture is one of a dynamic family of receptors than can be expressed in different states of activation. Alterations in activity are apparently mediated by conformational changes that can be induced from both outside and inside cells. In turn, these changes in activity have concomitant consequences for adhesion and signalling.