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

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

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.

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