Canonical Wnt signaling negatively regulates platelet function.

Abstract:

:Wnts regulate important intracellular signaling events, and dysregulation of the Wnt pathway has been linked to human disease. Here, we uncover numerous Wnt canonical effectors in human platelets where Wnts, their receptors, and downstream signaling components have not been previously described. We demonstrate that the Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion, and aggregation. Wnt3a also altered platelet shape change and inhibited the activation of the small GTPase RhoA. In addition, we found the Wnt-beta-catenin signaling pathway to be functional in platelets. Finally, disruption of the Wnt Frizzled 6 receptor in the mouse resulted in a hyperactivatory platelet phenotype and a reduced sensitivity to Wnt3a. Taken together our studies reveal a novel functional role for Wnt signaling in regulating anucleate platelet function and may provide a tractable target for future antiplatelet therapy.

authors

Steele BM,Harper MT,Macaulay IC,Morrell CN,Perez-Tamayo A,Foy M,Habas R,Poole AW,Fitzgerald DJ,Maguire PB

doi

10.1073/pnas.0906268106

subject

Has Abstract

pub_date

2009-11-24 00:00:00

pages

19836-41

issue

47

eissn

0027-8424

issn

1091-6490

pii

0906268106

journal_volume

106

pub_type

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