Integrins are conserved, cation-dependent transmembrane receptors essential for cell survival and growth, which are composed of an α and a β subunit that are differentially involved in ligand binding and connection with the cytoskeleton. They are specialized in linking cells to the extracellular matrix (ECM) and to cell surface-bound adhesion molecules, such as to allow cells to properly organize within tissues in relation to the underlying and/or surrounding matrices.
Thus, in epithelia and vasculature integrins are central elements in the structuring the intricate junctional complexes with the underlying basement membranes, whereas in connective tissues they allow the cells to form stable attachments (i.e. focal adhesions) with their surrounding interstitial matrices and rapidly convert (bidirectionally) from stationary to motile phenotypes. Integrins not engaged in ligand binding are generally dispersed on the surface of cells, but tend to form microclusters. Upon ligand engagement they reorganize to form larger clusters that permit the stabilization of the cell-ECM or cell-cell interactions.
Simultaneously, through phosphorylation of the cytoplasmic portion of the βsubunit, they associated with key cytoskeletal adapter proteins, such as vinculin, talin, paxillin, tensin and FAK and activate complex signal transduction pathways converging with those elicited by growth factor receptors and other receptors for soluble and membrane-bound signal molecules. This results in the activation of the cell cycle, cell differentiation programs and/or the acquisition of motile properties. Conversely, loss of integrin binding to the matrix causes a defined programmed cell death known as anoikis.
There are more than 15 αsubunits and 8 β subunits, which pair with each other in different combinations to generate a repertoire of over 20 different integrin receptors. These may other be selective for one or two ligands or being promiscuous, binding multiple ligands. Similarly, the same ECM component may be recognized by one individual integrin receptor or multiple receptors. Integrin expression is frequently altered in pathological conditions and mutations in the INTG genes are associated with inheritable diseases.
In cancer, integrins are fundamental in conferring a more aggressive behaviour to malignant cells and are therefore considered attractive therapeutic targets. However, thus far only one anti-integrin drug is registered for clinical application and its use is for the treatment of neurological rather rather neoplastic diseases.
Immunolabeling of human adult skin
Integrin α6 *The α6 integrin subunit pairs with two distinct βsubunit, β1 and β4, and with the latter one it forms a unique integrin receptor that is essential for the assembly and maintenance of hemidesmosomes. There are a total 8 different alternative spliced α6 isoforms known which show a diverse tissue distribution, i.e. isoforms containing segment X1 are ubiquitously expressed, whereas isoforms containing segment X1X2 are expressed in heart, kidney, placenta, colon, duodenum, myoblasts and myotubes. Similarly, in some tissues, isoforms containing cytoplasmic segment A and isoforms containing segment B are detected while in others, only isoforms containing one cytoplasmic segment are found.
Anti Integrin (ALPHA)6 (537D5)
To be used for research only. DO NOT use for human gene therapy or clinical diagnosis.