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Frizzled Proteins are bona fide G Protein-Coupled Receptors

Vladimir L. Katanaev¹ and Silke Buestorf¹

Correspondence: (Login to view email address)

1. Department of Biology, University of Konstanz

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Document Type:

Manuscript

Date:

Received 08 January 2009 16:38 UTC; Posted 09 January 2009

Subjects:

Cancer, Developmental Biology, Molecular Cell Biology, Pharmacology

Tags:

• G-protein coupled receptors
• heterotrimeric G proteins
• Frizzled
• wnt

Abstract:

Receptors of the Frizzled family initiate Wnt ligand-dependent signaling controlling
multiple steps in organism development and highly conserved in evolution.
Misactivation of the Wnt/Frizzled signaling is cancerogenic. Frizzled receptors
launch several signaling cascades: the canonical pathway regulating beta-catenin-dependent transcription; the planar cell polarity pathway polarizing the
cytoskeleton within the epithelial plane; and the calcium pathway. Frizzled
receptors possess seven transmembrane domains and their signaling depends on
trimeric G proteins in various organisms. However, Frizzleds constitute a
distinct group within the G protein-coupled receptors (GPCR) superfamily, and
Frizzled signaling can be G protein-independent in some experimental setups, which led to concerns about the GPCR nature of Frizzled. 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 Wnt antagonist) prevents Go activation, as does
pretreatment of Go with pertussis toxin. These experiments provide a biochemical
proof of the GPCR activities of Frizzled receptors and establish an in vitro assay to
monitor Frizzled activation by Wnt ligands, applicable for the high-throughput
agonist/antagonist screening.

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License:

This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Katanaev, Vladimir and Buestorf, Silke. Frizzled Proteins are bona fide G Protein-Coupled Receptors. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.2765.1> (2009)

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