integrin

Integrins are a family of heterodimeric transmembrane receptors that mediate cell adhesion to the extracellular matrix and to other cells, and that transduce signals in both directions across the plasma membrane. They are central to processes such as development, hemostasis, immune responses, wound healing, and angiogenesis.

Each integrin consists of an alpha and a beta subunit, noncovalently associated to form a functional receptor. In humans there are 18 alpha and 8 beta subunits, which can pair to produce at least 24 distinct integrins. Subunits contain a large extracellular domain that recognizes ligands, a single transmembrane helix, and a short cytoplasmic tail. Ligand binding occurs to a variety of ECM components, including fibronectin, vitronectin, collagen, and laminin, as well as to cell-surface ligands such as ICAMs and VCAMs. The specific alpha-beta combination determines tissue distribution and functional properties.

Integrins can be activated from inside the cell (inside-out signaling) by cytoplasmic proteins such as talin and kindlins, which increase affinity for ligands. Ligand engagement also triggers outside-in signaling, promoting focal adhesion formation and activation of kinases including FAK and Src, and downstream pathways such as PI3K/Akt and MAPK. This bidirectional signaling links mechanical cues from the extracellular environment to the cytoskeleton and gene expression.

Physiological roles span platelet aggregation (e.g., αIIbβ3), leukocyte trafficking (e.g., α4β1, α4β7), angiogenesis, and tissue integrity. Clinically, defects in integrins can cause leukocyte adhesion deficiencies; integrin antagonists such as natalizumab and vedolizumab target specific integrins in autoimmune diseases, while anti-platelet integrin inhibitors reduce thrombosis with bleeding risk as a consideration.