Title
The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system
UMMS Affiliation
Department of Pediatrics
Publication Date
2000-11
Document Type
Article
Subjects
Animals; Blood Platelets; Humans; Mice; Platelet Glycoprotein GPIb-IX Complex; *Platelet Membrane Glycoproteins; Receptors, Thrombin; Signal Transduction; Thrombin; von Willebrand Factor
Disciplines
Hematology | Oncology | Pediatrics
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.
Source
Thromb Haemost. 2000 Nov;84(5):897-903.
Journal/Book/Conference Title
Thrombosis and haemostasis
Related Resources
PubMed ID
11127874
Repository Citation
Furman MI, Nurden P, Berndt MC, Nurden AT, Benoit SE, Barnard MR, Ofosu FA, Michelson AD. (2000). The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system. Hematology/Oncology. Retrieved from https://escholarship.umassmed.edu/peds_hematology/22