Focal adhesions and integrin-mediated cell signaling

Publisher Summary Cells secrete, adhere to, and model arrays of extracellular matrix (ECM). The ECM affects many aspects of cell behavior, including their migratory properties, their growth and differentiation. It has been known for some time that addition of the ECM protein, fibronectin, and too many transformed cells in culture will restore a normal phenotype. These effects of fibronectin are due largely to its action of promoting or stabilizing focal adhesions. Under most conditions of cell culture, the surface to which cells adhere is a layer of ECM protein, usually fibronectin or vitronectin derived from serum, adsorbed to the plastic culture dish. Members of the integrin family of ECM receptors are concentrated at focal adhesions and form a transmembrane bridge between the ECM on the outside and the cytoskeleton on the inside. Focal adhesions are also regions of signal transduction between the ECM and the cytoplasm. The prominence of focal adhesions in many cultured cells probably reflects the abnormal conditions in which they are grown, in particular their growth on a rigid planar surface. Prominent components of focal adhesions are integrins, cell surface receptors that mediate adhesion to ECM molecules. This chapter discusses ECM-cytoskeletal interactions, concentrating on integrins and focal adhesions. In addition, the chapter reviews the signaling events triggered by integrin-mediated cell adhesion.