title: Cadherin 6 has a functional role in platelet aggregation and thrombus formation.
abstract: OBJECTIVE
  Thrombosis occurs at sites of vascular injury when platelets adhere to subendothelial matrix proteins and to each other. Platelets express many surface receptor proteins, the function of several of these remains poorly characterized. Cadherin 6 is expressed on the platelet surface and contains an arginine-glycine-aspartic acid motif, suggesting that it might have a supportive role in thrombus formation. The aim of this study was to characterize the role of cadherin 6 in platelet function.
  
  
  RESULTS
  Platelet aggregation was inhibited by both antibodies and exogenous soluble cadherin 6. Platelet adhesion to immobilized cadherin 6 was inhibited by arginine-glycine-aspartic acid-serine tetrapeptides. Antibodies to α(IIb)β(3) inhibited platelet adhesion to cadherin 6. Because platelet aggregation occurs in fibrinogen and von Willebrand factor double-deficient mice, we investigated whether cadherin 6 is an alternative ligand for the integrin α(IIb)β(3). Platelet aggregation in fibrinogen and von Willebrand factor double-deficient mice was significantly inhibited by an antibody to cadherin 6. In flow-based assays, inhibition of cadherin 6 caused a marked reduction in thrombus formation in both human and mouse blood.
  
  
  CONCLUSIONS
  This study demonstrates the role of cadherin 6 as a novel ligand for α(IIb)β(3) and highlights its function in thrombus formation.
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Eimear
authors.initials: E
authors.lastname: Dunne
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Spring
authors.forename: Adili
authors.initials: A
authors.lastname: Reheman
authors.forename: Wuxun
authors.initials: W
authors.lastname: Jin
authors.forename: Michael C
authors.initials: MC
authors.lastname: Berndt
authors.forename: Debra K
authors.initials: DK
authors.lastname: Newman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Newman
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.forename: Dermot
authors.initials: D
authors.lastname: Kenny
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D015820:Cadherins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000502:physiology; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology*
chemical_list: D015820:Cadherins; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid; C087310:K cadherin