GPIB

Glycoprotein Ib (GPIb) refers to a component of the platelet surface receptor complex GPIb-IX-V, which mediates primary platelet adhesion to damaged vascular subendothelium. The GPIb-IX-V complex is composed of four subunits: GPIbα (GP1BA), GPIbβ (GP1BB), GPIX (GP9), and GPV (GP5). GPIbα is the principal subunit that binds von Willebrand factor (vWF), with the other subunits helping to stabilize and assemble the complex on the platelet membrane.

Functionally, GPIb-IX-V captures platelets from flowing blood by binding to the A1 domain of immobilized or tethered vWF, especially under high shear conditions. This interaction mediates platelet tethering and rolling at injury sites and initiates intracellular signaling that promotes platelet activation and the stabilization of adhesion via integrins such as αIIbβ3 (GPIIb-IIIa). The signaling pathways involve associated cytoplasmic proteins and kinases that coordinate cytoskeletal rearrangements.

Genetic and clinical aspects: Defects in any component of the GPIb-IX-V complex can cause Bernard-Soulier syndrome, a rare autosomal recessive bleeding disorder characterized by macrothrombocytopenia and markedly abnormal ristocetin-induced platelet agglutination. Diagnosis typically shows reduced GPIb expression on platelets and defective ristocetin responses. Autoantibodies against GPIb-IX-V can also occur in immune thrombocytopenia, contributing to platelet destruction.

GPIb remains a key player in hemostasis through its role in initial platelet capture at sites of vascular injury, working in concert with other platelet receptors to promote stable thrombus formation.