integrins

Integrins are a family of transmembrane receptor proteins that mediate adhesion between cells and the extracellular matrix (ECM) or other cells, and that also transduce signals into the cell. They function as heterodimers composed of one α and one β subunit, and through combinations of subunits form at least 24 distinct integrins in humans. Integrins can bind a variety of ECM proteins, including fibronectin, collagen, laminin, and vitronectin, enabling cells to attach, spread, and migrate.

The adhesion and signaling activities of integrins depend on their conformational state. Inactive integrins have a bent conformation with low affinity for ligands; upon activation, they extend and increase ligand-binding affinity. Inside-out signaling, often initiated by cytoskeletal adaptors such as talin and kindlin binding to the β-subunit tail, promotes activation. Outside-in signaling occurs when ligand binding transmits signals into the cell, influencing cytoskeletal organization and gene expression.

Signaling associated with integrins involves focal adhesions and kinases such as FAK and Src, along with downstream pathways including PI3K/Akt and MAPK. These signals coordinate cell adhesion, migration, proliferation, survival, and differentiation. Integrins also play critical roles in immune cell trafficking and platelet aggregation, contributing to hemostasis and inflammation.

Clinical relevance includes associations with cancer metastasis, inflammatory diseases, and fibrosis. Therapeutic approaches include integrin antagonists and monoclonal antibodies, such as abciximab targeting αIIbβ3 to prevent thrombosis, natalizumab targeting α4-containing integrins for multiple sclerosis, and vedolizumab targeting α4β7 for inflammatory bowel disease.