WNT-5A stimulates the GDP/GTP exchange at pertussis toxin-sensitive heterotrimeric G proteins

Cell Signal. 2011 Mar;23(3):550-4. doi: 10.1016/j.cellsig.2010.11.004. Epub 2010 Nov 8.


The lipoglycoproteins of the WNT family act on seven transmembrane-spanning Class Frizzled receptors. Here, we show that WNT-5A evokes a proliferative response in a mouse microglia-like cell line (N13), which is sensitive to pertussis toxin, thus implicating the involvement of heterotrimeric G proteins of the G(i/o) family. We continue to show that WNT-5A stimulation of N13 membranes and permeabilized cells evokes the exchange of GDP for GTP of pertussis toxin-sensitive G proteins employing [γ-(35)S]GTP assay and activity state-specific antibodies to GTP-bound G(i) proteins. Our functional analysis of the PTX-sensitivity of WNT-induced G protein activation and PCR analysis of G protein and FZD expression patterns suggest that WNT-5A stimulation leads to the activation of G(i2/3) proteins in N13 cells possibly mediated by FZD(5), the predominant FZD expressed. In summary, we provide for the first time molecular proof that WNT-5A stimulation results in the activation of heterotrimeric G(i2/3) proteins in mammalian cells with physiological protein stochiometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation
  • Guanosine Diphosphate / metabolism*
  • Guanosine Triphosphate / metabolism*
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Mice
  • Pertussis Toxin / pharmacology*
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction
  • Wnt Proteins / physiology*
  • Wnt-5a Protein


  • Receptors, Cell Surface
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • pertussis toxin receptor
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Pertussis Toxin
  • Heterotrimeric GTP-Binding Proteins