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.
journal_name
Proc Natl Acad Sci U S Aauthors
Steele BM,Harper MT,Macaulay IC,Morrell CN,Perez-Tamayo A,Foy M,Habas R,Poole AW,Fitzgerald DJ,Maguire PBdoi
10.1073/pnas.0906268106subject
Has Abstractpub_date
2009-11-24 00:00:00pages
19836-41issue
47eissn
0027-8424issn
1091-6490pii
0906268106journal_volume
106pub_type
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