Integrines

Integrins are a family of transmembrane receptors that mediate adhesion between cells and the extracellular matrix (ECM) or between neighboring cells. They function as heterodimers composed of one alpha and one beta subunit. In humans, 18 alpha and 8 beta subunits assemble into at least 24 distinct integrins, each with specific ligand preferences. The extracellular domains of integrins recognize ECM proteins such as fibronectin, collagen, laminin, and vitronectin; some subtypes bind to the RGD motif, while others recognize different sequences.

Integrins also connect to the actin cytoskeleton inside the cell via adaptor proteins including talin and kindlin, forming focal adhesions. Activation occurs through inside-out signaling, in which signals such as chemokines or cytoplasmic proteins induce conformational changes that increase affinity. Engagement with ECM ligands triggers outside-in signaling, activating kinases such as focal adhesion kinase (FAK) and Src, promoting cytoskeletal rearrangements, cell migration, proliferation, survival, and gene expression. Integrins can cluster to strengthen adhesion and coordinate communication between the cell interior and its external environment.

Biological roles include embryonic development, wound healing, immune cell trafficking, and platelet aggregation, where αIIbβ3 mediates platelet aggregation and is a common therapeutic target. Dysregulation of integrin signaling is linked to cancer metastasis, fibrosis, and inflammatory diseases. Genetic deficiencies in integrins, such as mutations in ITGB2 causing leukocyte adhesion deficiency type I (LAD-1), impair immune cell adhesion. Therapeutic approaches include integrin-blocking antibodies and small molecules to modulate adhesion and signaling in various diseases.