integrina

Integrinas, or integrins, are a family of transmembrane receptors that mediate adhesion between cells and the extracellular matrix, as well as between neighboring cells. They play essential roles in development, immune responses, wound healing, and tissue homeostasis.

Each integrin is a heterodimer formed by one α subunit and one β subunit. In humans, there are 18 α and 8 β subunits, enabling at least 24 distinct heterodimeric receptors, such as α5β1, αvβ3, and the platelet-specific αIIbβ3. The extracellular domain binds ligands, while the cytoplasmic tails interact with the cytoskeleton and signaling proteins.

Integrins exist in low-affinity and high-affinity states. Activation, or inside-out signaling, is driven by cytoplasmic proteins like talin and kindlin linking to the β tail, which increases ligand-binding affinity. Extracellular binding is modulated by divalent cations, with Mg2+ and Mn2+ promoting adhesion.

Ligands include extracellular matrix proteins such as fibronectin, laminin, collagen, and vitronectin. Many integrins recognize the RGD (arginine-glycine-aspartate) motif in ligands, though some bind different sequences. Through ligand binding and clustering, integrins form focal adhesions that connect to the actin cytoskeleton and initiate signaling cascades.

Biological roles of integrins are diverse: they regulate cell adhesion and migration, influence survival, proliferation, and differentiation, and participate in immune cell trafficking, platelet aggregation, angiogenesis, and tissue remodeling. They are critical for development and homeostasis, and their dysregulation is linked to cancer, fibrosis, and inflammatory diseases.

Therapeutically, integrins are targeted in cancer, autoimmune disorders, and cardiovascular disease. Approaches include monoclonal antibodies and small-molecule inhibitors that selectively target specific integrin subtypes, some of which are approved or approved in clinical trials.