Integrin

The integrins are a superfamily of cell adhesion receptors (cell adhesion molecules, CAMs) that bind to a wide variety of ligands in the extracellular matrix, on the surface of other cells and also soluble proteins. Integrins are restricted to the metazoa; no homologs are detected in prokaryotes, plants, or fungi. Integrins are type I membrane proteins that are large heterodimers consisting of α- and β-chains. In vertebrates, the family is composed of 18 α subunits and 8 β subunits that can assemble into 24 different heterodimers. The α- and β-chains are totally distinct, with no detectable homology between them; sequence identity among α subunits is about 30% and among β subunits 45%. The integrins are expressed in a cell- and tissue-specific manner and can be grouped into subgroups based on ligand-binding properties or based on their subunit composition. Integrin heterodimers can adopt a bent or closed conformation that has a low affinity for ligand (‘inactive’) or an extended or open conformation that has a high affinity for ligand (‘active’). As a consequence of this conformational switching, integrins are able to signal bidirectionally across the membrane: ligand binding elicits signalling responses within the cell (‘outside-in’ signalling), but binding of intracellular proteins such as talin and kindlins to integrins regulates the activation of integrins to promote ligand-binding (‘inside-out’ signalling). Integrins are able to control diverse cellular processes, including proliferation, apoptosis, differentiation and cell migration and thus have key roles in development, immune responses and the progression of diseases such as cancer.