title: Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and Do not exhibit a Bernard-Soulier phenotype.
abstract: Adhesion of platelets to extracellular matrix via von Willebrand factor (vWF) and activation of platelets by thrombin are critical steps in hemostasis. Glycoprotein (GP) V is a component of the GPIb-V-IX complex, the platelet receptor for vWF. GPV is also cleaved by thrombin. Deficiency of GPIb or GPIX results in Bernard-Soulier syndrome (BSS), a bleeding disorder in which platelets are giant and have multiple functional defects. Whether GPV-deficiency might also cause BSS is unknown as are the roles of GPV in platelet-vWF interaction and thrombin signaling. We report that GPV-deficient mice developed normally, had no evidence of spontaneous bleeding, and had tail bleeding times that were not prolonged compared with wild-type mice. GPV-deficient platelets were normal in size and structure as assessed by flow cytometry and electron microscopy. GPV-deficient and wild-type platelets were indistinguishable in botrocetin-mediated platelet agglutination and in their ability to adhere to mouse vWF A1 domain. Platelet aggregation and ATP secretion in response to low and high concentrations of thrombin were not decreased in GPV-deficient platelets compared with wild-type. Our results show that (1) GPV is not necessary for GPIb expression and function in platelets and that GPV deficiency is not likely to be a cause of human BSS and (2) GPV is not necessary for robust thrombin signaling. Whether redundancy accounts for the lack of phenotype of GPV-deficiency or whether GPV serves subtle or as yet unprobed functions in platelets or other cells remains to be determined.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Kahn
authors.forename: T G
authors.initials: TG
authors.lastname: Diacovo
authors.forename: D F
authors.initials: DF
authors.lastname: Bainton
authors.forename: F
authors.initials: F
authors.lastname: Lanza
authors.forename: J
authors.initials: J
authors.lastname: Trejo
authors.forename: S R
authors.initials: SR
authors.lastname: Coughlin
mesh_terms: D000818:Animals; D001606:Bernard-Soulier Syndrome / Q000097:blood* / Q000235:genetics; D001792:Blood Platelets / Q000502:physiology*; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D006490:Hemostatics; D019038:Platelet Glycoprotein GPIb-IX Complex; D013917:Thrombin