Platelet physiology and thrombosis

• Published in: Thrombosis research 2004, Vol.114 (5), p.447-453
• Main Authors: Andrews, Robert K., Berndt, Michael C.
• Format: Article
• Language: English
• Subjects: ADAM Proteins; ADAMTS13 Protein; Binding Sites; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood Platelets - cytology; Blood Platelets - physiology; Blood vessels and receptors; Cardiology. Vascular system; Collagen - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Disulfides - metabolism; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Fibrinogen - metabolism; Fundamental and applied biological sciences. Psychology; Glycoprotein; Humans; Leucine - chemistry; Ligands; Macrophage-1 Antigen - chemistry; Medical sciences; Metalloendopeptidases - metabolism; Models, Biological; Molecular and cellular biology; P-selectin; P-Selectin - chemistry; Platelet; Platelet Activation; Platelet Adhesiveness; Platelet Glycoprotein GPIb-IX Complex - metabolism; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Protein Binding; Protein Structure, Tertiary; Thrombosis - blood; Thrombus formation; Vertebrates: cardiovascular system; von Willebrand Factor - metabolism
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2004.07.020

Glycoprotein (GP) Ibα of the GPIb-IX–V complex and GPVI bind von Willebrand factor (vWF) and collagen, respectively, and are critical for the initial interaction of circulating platelets with the injured vessel wall under high shear conditions. These interactions act together to facilitate stable thrombus formation in vivo. Ligand binding to GPIb-IX–V of the leucine-rich repeat family or GPVI of the immunoglobulin superfamily initiates platelet activation, and inside–out activation of the platelet integrin, αIIbβ3, that binds vWF or fibrinogen and mediates platelet aggregation. The binding site for GPIbα on vWF resides in the conserved A1 domain, encompassing the disulfide bond at Cys509–Cys695. This domain may be activated to bind platelet GPIbα under shear stress by anchoring of the downstream A3 domain to collagen and conformational distortion of the intervening A2 domain. The N-terminal, 282 residues, of GPIbα contains the binding site for vWF-A1, as well as the conserved A-type domain of the leukocyte integrin αMβ2 (αM I domain) and P-selectin expressed on activated platelets or endothelial cells. Endothelial P-selectin also supports surface expression of vWF multimers, enabling platelet vessel wall interaction by at least two mechanisms. Recent evidence suggests GPVI that binds collagen, and GPIb-IX–V that binds collagen-bound vWF are physically associated on the platelet surface. This review will focus on the structure–function of primary platelet adhesion receptors, GPIb-IX–V and GPVI, and how they act together to regulate platelet thrombus formation in pathophysiology.