Integralins

Integralins are a family of heterodimeric transmembrane receptors that mediate adhesion between cells and the extracellular matrix or other cells. Composed of alpha and beta subunits that noncovalently associate, integrins transduce signals in both directions, linking the extracellular environment to intracellular signaling and cytoskeletal organization.

In humans there are 18 alpha and 8 beta subunits, producing at least 24 distinct heterodimers with tissue-specific distributions and ligand specificities. Ligands include extracellular matrix proteins such as fibronectin, collagen, and laminin; some integrins also bind to cell surface counter-receptors and other ligands, often recognizing the RGD motif in extracellular matrix proteins.

Integrins exist in low- to high-affinity conformations. Inside-out activation, driven by cytoplasmic proteins such as talin and kindlin binding to the beta tail, induces a conformational change to a high-affinity state that can capture ligands. Outside-in signaling begins after ligand binding and activates intracellular pathways involving focal adhesion kinase (FAK), Src family kinases, PI3K, and MAPKs, influencing adhesion, migration, proliferation, and survival.

Physiological roles include development, hemostasis, immune cell trafficking, wound healing, and angiogenesis. In disease, integrins contribute to tumor invasion and metastasis, fibrosis, and chronic inflammatory conditions. The mechanical features of integrin signaling also integrate with growth factor receptors and cytoskeletal mechanics.

Integrins are targets of therapeutic agents, including antibodies and small molecules. Examples include abciximab and eptifibatide (GPIIb/IIIa, αIIbβ3) for antiplatelet therapy; vedolizumab (α4β7) and natalizumab (α4-containing integrins) for inflammatory bowel disease and multiple sclerosis; and research continues on integrin inhibitors for cancer and fibrosis.