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.
Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / metabolism
-
Blood Platelets / cytology
-
Blood Platelets / metabolism*
-
Densitometry / methods
-
Extracellular Matrix / metabolism
-
Gene Expression Regulation*
-
Guanosine Triphosphate / chemistry
-
Humans
-
Hydrolysis
-
Microfilament Proteins
-
Models, Biological
-
Monomeric GTP-Binding Proteins / metabolism*
-
Recombinant Proteins / metabolism
-
Signal Transduction
-
Wnt3A Protein / metabolism*
-
cdc42 GTP-Binding Protein / metabolism
-
rac1 GTP-Binding Protein / metabolism
-
rap GTP-Binding Proteins / metabolism
-
rho GTP-Binding Proteins
Substances
-
Adaptor Proteins, Signal Transducing
-
DAAM1 protein, human
-
Microfilament Proteins
-
Recombinant Proteins
-
Wnt3A Protein
-
Guanosine Triphosphate
-
RAP1B protein, human
-
Monomeric GTP-Binding Proteins
-
cdc42 GTP-Binding Protein
-
rac1 GTP-Binding Protein
-
rap GTP-Binding Proteins
-
rho GTP-Binding Proteins