Frizzled receptors signal through G proteins

Andrea S. Nichols, Desiree H. Floyd, Stephen P. Bruinsma, Kirk Narzinski, Thomas J. Baranski

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Frizzled receptors have long been thought to couple to G proteins but biochemical evidence supporting such an interaction has been lacking. Here we expressed mammalian Wnt-Frizzled fusion proteins in Saccharomyces cerevisiae and tested the receptors' ability to activate the yeast mitogen-activated protein kinase (MAPK) pathway via heterotrimeric G proteins. Our results show that Frizzled receptors can interact with Gαi, Gαq, and Gαs proteins, thus confirming that Frizzled functions as a G protein coupled receptor (GPCR). However, the activity level of Frizzled-mediated G protein signaling was much lower than that of a typical GPCR and, surprisingly, was highest when coupled to Gαs. The Frizzled/Gαs interaction was further established in vivo as Drosophila expressing a loss-of-function Gαs allele rescued the photoreceptor differentiation phenotype of Frizzled mutant flies. Together, these data point to an important role for Frizzled as a nontraditional GPCR that preferentially couples to Gαs heterotrimeric G proteins.

Original languageEnglish
Pages (from-to)1468-1475
Number of pages8
JournalCellular Signalling
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Frizzled
  • G protein
  • GDI
  • GPCR
  • Planar cell polarity
  • Wnt signaling

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