Integrin Signaling & Focal Adhesions
Cell-ECM adhesion receptors transducing mechanical and chemical signals.
Overview
Integrins are αβ heterodimeric transmembrane receptors that connect the extracellular matrix (ECM) to the actin cytoskeleton. Upon ligand binding (fibronectin, collagen, laminin), integrins cluster and recruit scaffolding proteins (talin, kindlin, vinculin, paxillin) to form focal adhesions. FAK autophosphorylation recruits Src kinase, activating downstream RAS-MAPK, PI3K-AKT, and Rho GTPase pathways. Integrins exhibit bidirectional signaling: outside-in (ECM → cell) and inside-out (cell activation state → integrin affinity).
Cellular Location
Cell-ECM interface, focal adhesions
Clinical Significance
αIIbβ3 integrin on platelets mediates clot formation (target of abciximab, eptifibatide); α4 integrins in immune cell trafficking (natalizumab for MS); tumor invasion requires integrin-ECM interactions.