The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system
Department of Pediatrics
Medical Subject Headings
Animals; Blood Platelets; Humans; Mice; Platelet Glycoprotein GPIb-IX Complex; *Platelet Membrane Glycoproteins; Receptors, Thrombin; Signal Transduction; Thrombin; von Willebrand Factor
Hematology | Oncology | Pediatrics
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.
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Citation: Thromb Haemost. 2000 Nov;84(5):897-903.
Furman, Mark I.; Nurden, Pauita; Berndt, Michael C.; Nurden, Alan T.; Benoit, Stephen E.; Barnard, Marc R.; Ofosu, Frederick A.; and Michelson, Alan D., "The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system" (2000). Hematology/Oncology. 22.