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28. Platelet Receptor Structures and Polymorphisms
Efficient platelet cohesion (i.e., platelet aggregation) is necessary for the life-saving process of hemostasis. Plaque rupture and/or endothelial damage lead to exposure of collagens, retention of von Willebrand factor (vWF), and the adhesion of circulating platelets to the damaged vessel wall through the concerted participation of a handful of important receptors. With blood flow conditions ranging from low shear (≤300 s) to high shear (≥1500 s), the initial transient arrest of platelets on collagen requires vWF acting as a bridge between collagen and the glycoprotein (GP) Ib complex (1,2). Although not usually considered a collagen receptor, the GPIb complex does initiate the first adhesive platelet contact with the collagen-rich matrix. It is collagen that captures the vWF molecule by binding to its A3 domain, thereby localizing it and somehow altering its conformation to make it bind via its A1 domain with greater avidity to the GPIb complex. This interaction is relatively weak and short in duration, resulting in a slowing of platelet motion and a tethering or rolling of the platelet across the thrombo-genic collagen-rich surface. Nonetheless, the GPIb complex plays an important role in signal transduction, which activates, in part, other platelet receptors, particularly the integrins α2β1 and αIIbβ3. Blockade of vWF binding to the GPIb complex will inhibit this initial contact, and stable platelet monolayer formation and thrombus formation would then not ensue.
Affiliation(s): (1) Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA
(2) DNA Array Core Facility, Department of Research Resources, The Scripps Research Institute, La Jolla, CA
(3) Division of Experimental Hemostasis & Thrombosis, Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, CA
Series: Methods in Molecular Biology  |  Volume: 273  |  Pub. Date: Aug-13-2004  |  Page Range: 455-478  |  DOI: 10.1385/1-59259-783-1:455
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