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PMID:19901330

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Citation

Steele, BM, Harper, MT, Macaulay, IC, Morrell, CN, Perez-Tamayo, A, Foy, M, Habas, R, Poole, AW, Fitzgerald, DJ and Maguire, PB (2009) Canonical Wnt signaling negatively regulates platelet function. Proc. Natl. Acad. Sci. U.S.A. 106:19836-41

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.

Links

PubMed PMC2785253 Online version:10.1073/pnas.0906268106

Keywords

Animals; Blood Platelets/cytology; Blood Platelets/metabolism; Calcium/metabolism; Enzyme Activation; Frizzled Receptors/metabolism; Humans; Mice; Platelet Adhesiveness/physiology; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism; Receptors, G-Protein-Coupled/metabolism; Secretory Vesicles/metabolism; Signal Transduction/physiology; Wnt Proteins/metabolism; Wnt3 Protein; Wnt3A Protein; beta Catenin/metabolism; rhoA GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FZD6

acts_upstream_of_or_within

GO:0030168: platelet activation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3050103

P

Seeded From UniProt

complete

MOUSE:WNT3A

acts_upstream_of_or_within

GO:0030168: platelet activation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT3A

acts_upstream_of_or_within

GO:0070527: platelet aggregation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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