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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
› Author AffiliationsThe 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
Further Information

Publication History

Received 04 November 1999

Accepted after resubmission 02 May 2000

Publication Date:
13 December 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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