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

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Original title:WNT-5A stimulates the GDP/GTP exchange at pertussis toxin-sensitive heterotrimeric G proteins.
Authors:Michaela Kilander, Jacomijn P Dijksterhuis, Sri Ranjani Ganji, Vítězslav Bryja, Gunnar Schulte
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Original language:English
Field:Physiology
WWW:link to a new windowhttp://www.ncbi.nlm.nih.gov/pubmed/21070854
Type:Article in Periodical
Keywords:Frizzled; GPCR; G protein; [gamma-S]GTP; Non-canonical; WNT signaling

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 [gamma-(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.

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