The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system

Thromb Haemost. 2000 Nov;84(5):897-903.

Abstract

The only known function of the 41 amino acid cleaved peptide (TR1-41) of the seven transmembrane domain thrombin receptor (PARI) 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 GPIbalpha, and TM60, directed against the thrombin binding site on GPIbalpha). 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 GPIbalpha binding sites for von Willebrand factor and thrombin.

MeSH terms

  • Animals
  • Blood Platelets / metabolism*
  • Humans
  • Mice
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*
  • Platelet Membrane Glycoproteins*
  • Receptors, Thrombin / metabolism*
  • Signal Transduction
  • Thrombin / metabolism*
  • von Willebrand Factor / metabolism

Substances

  • Platelet Glycoprotein GPIb-IX Complex
  • Platelet Membrane Glycoproteins
  • Receptors, Thrombin
  • glycoprotein receptor GPIb-IX
  • von Willebrand Factor
  • Thrombin