Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling

Diane C Slusarski; Victor G Corces; Randall T Moon

doi:10.1038/37138

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Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling

Journal article

Peer reviewed

Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling

Diane C Slusarski, Victor G Corces and Randall T Moon

Nature (London), Vol.390(6658), pp.410-413

11/27/1997

DOI: 10.1038/37138

PMID: 9389482

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Abstract

In Drosophila, members of the frizzled family of tissue-polarity genes encode proteins that are likely to function as cell-surface receptors of the type known as Wnt receptors, and to initiate signal transduction across the cell membrane, although how they do this is unclear. We show here that the rat protein Frizzled-2 causes an increase in the release of intracellular calcium which is enhanced by Xwnt-5a, a member of the Wnt family. This release of intracellular calcium is suppressed by an inhibitor of the enzyme inositol monophosphatase and hence of the phosphatidylinositol signalling pathway; this suppression can be rescued by injection of the compound myo-inositol, which overcomes the decrease in this intermediate caused by the inhibitor. Agents that inhibit specific G-protein subunits, pertussis toxin, GDP-beta-S and alpha-transducin also inhibit the calcium release triggered by Xwnt-5a and rat Frizzled-2. Our results indicate that some Wnt proteins work through specific Frizzled homologues to stimulate the phosphatidylinositol signalling pathway via heterotrimeric G-protein subunits.

GTP-Binding Proteins - drug effects

Calcium - metabolism

Humans

Wnt Proteins

Virulence Factors, Bordetella - pharmacology

Wnt-5a Protein

Receptors, Neurotransmitter - genetics

Phosphatidylinositols - metabolism

Guanosine Diphosphate - pharmacology

Phosphoric Monoester Hydrolases - antagonists & inhibitors

Frizzled Receptors

Enzyme Inhibitors - pharmacology

Receptors, G-Protein-Coupled

Pertussis Toxin

Rats

Zebrafish

Recombinant Proteins - pharmacology

Thionucleotides - pharmacology

Xenopus Proteins

Animals

Proteins - metabolism

Guanosine Diphosphate - analogs & derivatives

Signal Transduction - drug effects

Embryo, Nonmammalian

Receptors, Neurotransmitter - metabolism

Diphosphonates - pharmacology

GTP-Binding Proteins - metabolism

Details

Title: Subtitle: Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling
Creators: Diane C Slusarski - Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA
Victor G Corces
Randall T Moon
Resource Type: Journal article
Publication Details: Nature (London), Vol.390(6658), pp.410-413
Publisher: England
DOI: 10.1038/37138
PMID: 9389482
ISSN: 0028-0836
eISSN: 1476-4687
Language: English
Date published: 11/27/1997
Academic Unit: Biology
Record Identifier: 9983992093502771

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