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Frizzled receptors signal through G proteins.

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 G?i, G?q, and G?s 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 G?s. The Frizzled/G?s interaction was further established in vivo as Drosophila expressing a loss-of-function G?s 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 G?s heterotrimeric G proteins.

SUBMITTER: Nichols AS

PROVIDER: S-EPMC3640709 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Frizzled receptors signal through G proteins.

Nichols Andrea S AS Floyd Desiree H DH Bruinsma Stephen P SP Narzinski Kirk K Baranski Thomas J TJ

Cellular signalling 20130319 6

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 protei ...[more]

PMID: 23524329

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