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Thromb Haemost 2000; 84(05): 897-903
DOI: 10.1055/s-0037-1614134
Review Article
Schattauer GmbH

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   From the Center for Platelet Function Studies, Division of Cardiovascular Medicine, Department of Medicine, UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, Massachusetts, USA
,
Paquita Nurden
2   UMR 5533 CNRS, Hopital Cardiologique, Pessac, France
,
Michael C. Berndt
3   Baker Medical Research Institute, Prahran, Australia
,
Alan T. Nurden
2   UMR 5533 CNRS, Hopital Cardiologique, Pessac, France
,
Stephen E. Benoit
1   From the Center for Platelet Function Studies, Division of Cardiovascular Medicine, Department of Medicine, UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, Massachusetts, USA
4   Center for Platelet Function Studies, Department of Pediatrics, UMass Memorial Health Care, University of Massachusetts Medical School, orcester, Massachusetts, USA
,
Marc R. Barnard
4   Center for Platelet Function Studies, Department of Pediatrics, UMass Memorial Health Care, University of Massachusetts Medical School, orcester, Massachusetts, USA
,
Frederick A. Ofosu
5   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
,
Alan D. Michelson
4   Center for Platelet Function Studies, Department of Pediatrics, UMass Memorial Health Care, University of Massachusetts Medical School, orcester, Massachusetts, USA
› InstitutsangabenThe authors thank Drs. Barry S. Coller, Federico Garrido, Thomas J. Kunicki, Changgeng Ruan, Qi-Hong Sun, Albert E. G. Kr. von dem Borne, and Naomasa Yamamoto for generously providing monoclonal antibodies
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Publikationsverlauf

Received 04. November 1999

Accepted after resubmission 02. Mai 2000

Publikationsdatum:
13. Dezember 2017 (online)

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Summary

The only known function of the 41 amino acid cleaved peptide (TR1-41) 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 TR1-41 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 GPIbα, and TM60, directed against the thrombin binding site on GPIbα). TR1-41 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, TR1-41 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 (TR1-41) of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the SCCS, thereby negatively regulating the GPIbα binding sites for von Willebrand factor and thrombin.

Key words

Thrombin - thrombin receptor - von Willebrand factor - peptide - flow cytometry
 

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