Signal transduction via integrin adhesion complexes.

Integrin adhesion complexes (IACs) have evolved over millions of years to integrate metazoan cells physically with their microenvironment. It is presumed that the simultaneous interaction of thousands of integrin receptors to binding sites in anisotropic extracellular matrix (ECM) networks enables cells to assemble a topological description of the chemical and mechanical properties of their surroundings. This information is then converted into intracellular signals that influence cell positioning, differentiation and growth, but may also influence other fundamental processes, such as protein synthesis and energy regulation. In this way, changes in the microenvironment can influence all aspects of cell phenotype. Current concepts envisage cell fate decisions being controlled by the integrated signalling output of myriad receptor clusters, but the mechanisms are not understood. Analyses of the adhesome, the complement of proteins attracted to the vicinity of IACs, are now providing insights into some of the primordial links connecting these processes. This article reviews recent advances in our understanding of the composition of IACs, the mechanisms used to transduce signals through these junctions, and the links between IACs and cell phenotype.