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FEBS Lett. 2012 Jul 30;586(16):2267-72. doi: 10.1016/j.febslet.2012.05.060. Epub 2012 Jun 13.

WNT-3a modulates platelet function by regulating small GTPase activity.

Author information

1
UCD Conway Institute, University College Dublin, Belfield, Dublin D4, Ireland. brian.steele@ucd.ie

Abstract

Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)β(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.

PMID:
22705156
DOI:
10.1016/j.febslet.2012.05.060
[Indexed for MEDLINE]
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