Canonical Wnt signaling negatively regulates platelet function

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

Research output: Contribution to journalArticle (Academic Journal)peer-review

43 Citations (Scopus)

Abstract

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.
Translated title of the contributionCanonical Wnt signaling negatively regulates platelet function
Original languageEnglish
Pages (from-to)19836 - 19841
JournalProceedings of the National Academy of Sciences of the United States of America
Volume160(47)
Publication statusPublished - Nov 2009

Bibliographical note

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

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