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The Cleaved Peptide of PAR1 Results in a Redistribution of the Platelet Surface GPIb-IX-V Complex to the Surface-Connected Canalicular System

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2000: 84/5 (Nov) pp.740-934
Pages: 897-903

The Cleaved Peptide of PAR1 Results in a Redistribution of the Platelet Surface GPIb-IX-V Complex to the Surface-Connected Canalicular System

Mark I. Furman (1) , Paquita Nurden (2) , Michael C. Berndt (3) , Alan T. Nurden (2) , Stephen E. Benoit (1), (4) , Marc R. Barnard (4) , Frederick A. Ofosu (5) , Alan D. Michelson (4)
From the (1) Center for Platelet Function Studies, Division of Cardiovascular Medicine, Department of Medicine, UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, Massachusetts, USA; (2) UMR 5533 CNRS, Hopital Cardiologiq

Summary

The only known function of the 41 amino acid cleaved peptide (TR 1-41 ) of the seven transmembrane domain thrombin receptor (PAR1) is to activate platelets (as determined by aggregation, surface P-selectin, and fibrinogen binding to activated GPIIb-IIIa). We now demonstrate that TR 1-41 results in a concentration-dependent decrease in the platelet surface expression of each component of the GPIb-IX-V complex, as determined by flow cytometry with a panel of monoclonal antibodies (including 6D1, directed against the von Willebrand factor binding site on GPIb, and TM60, directed against the thrombin binding site on GPIb). TR 1-41 also decreased ristocetin-induced platelet agglutination. Immunoblotting after incubation of platelets with TR1-41 revealed neither a loss of platelet GPIb nor increase in supernatant GPIb fragments. As demonstrated by immunoelectron microscopy, TR 1-41 resulted in a redistribution of GPIb, GPIX, and GPV from the platelet surface to the surface-connected canalicular system (SCCS). In summary, the cleaved peptide (TR 1-41 ) of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the SCCS, thereby negatively regulating the GPIbbinding sites for von Willebrand factor and thrombin.

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