Volume 7 Supplement 1

12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes

Open Access

The G protein-coupled receptor identity of the frizzled proteins

  • VL Katanaev1 and
  • S Buestorf1
Cell Communication and Signaling20097(Suppl 1):A19

DOI: 10.1186/1478-811X-7-S1-A19

Published: 26 February 2009

Receptors of the Frizzled family initiate Wnt ligand-dependent signal transduction cascades controlling multiple steps in organism development and are highly conserved in animal evolution. Misactivation of the Wnt/Frizzled signaling underlies many cases of cancerogenesis. Frizzled receptors possess seven transmembrane domains and their signaling depends on trimeric G proteins in various organisms. However, as Frizzled proteins constitute a distinct group within the superfamily of G protein-coupled receptors (GPCR), and as Frizzled signaling can apparently be G protein-independent in some experimental setups, the GPCR nature of Frizzled receptors has been questioned. Here we demonstrate that human Frizzled receptors can directly bind the trimeric Go protein in a pertussis toxin-sensitive manner. Furthermore, addition of Wnt ligands elicits Frizzled-dependent guanine nucleotide exchange on Go. An excess of secreted Frizzled-related protein, a known antagonist of the Wnt/Frizzled pathways, inhibits Go activation, as does pretreatment of Go with pertussis toxin. These experiments provide a biochemical proof of the GPCR activities of Frizzled receptors. They also establish an in vitro assay of monitoring Frizzled activation by Wnt ligands, applicable for the high-throughput agonist/antagonist screening.

Authors’ Affiliations

(1)
Department of Biology, University of Konstanz

Copyright

© Katanaev and Buestorf; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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