The trimeric G protein Go inflicts a double impact on axin in the Wnt/frizzled signaling pathway.

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Version: Final published version
Serval ID
serval:BIB_AC1E648240D6
Type
Article: article from journal or magazin.
Collection
Publications
Title
The trimeric G protein Go inflicts a double impact on axin in the Wnt/frizzled signaling pathway.
Journal
Developmental Dynamics
Author(s)
Egger-Adam D., Katanaev V.L.
ISSN
1097-0177 (Electronic)
ISSN-L
1058-8388
Publication state
Published
Issued date
2010
Volume
239
Number
1
Pages
168-183
Language
english
Abstract
The Wnt/Frizzled signaling pathway plays crucial roles in animal development and is deregulated in many cases of carcinogenesis. We and others have previously demonstrated that Frizzled proteins initiating the intracellular signaling are typical G protein-coupled receptors and rely on the trimeric G protein Go for Wnt transduction in Drosophila. However, the mode of action of Go and its interplay with other transducers of the pathway such as Dishevelled and Axin remained unclear. Here we show that the alpha-subunit of Go directly acts on Axin, the multidomain protein playing a negative role in the Wnt signaling. G alpha o physically binds Axin and re-localizes it to the plasma membrane. Furthermore, G alpha o suppresses Axin's inhibitory action on the Wnt pathway in Drosophila wing development. The interaction of G alpha o with Axin critically depends on the RGS domain of the latter. Additionally, we show that the betagamma-component of Go can directly bind and recruit Dishevelled from cytoplasm to the plasma membrane, where activated Dishevelled can act on the DIX domain of Axin. Thus, the two components of the trimeric Go protein mediate a double-direct and indirect-impact on different regions of Axin, which likely serves to ensure a robust inhibition of this protein and transduction of the Wnt signal.
Keywords
Adaptor Proteins, Signal Transducing/genetics, Adaptor Proteins, Signal Transducing/metabolism, Animals, Axin Protein, Blotting, Western, Cell Membrane/metabolism, Cloning, Molecular, Drosophila/growth & development, Drosophila/metabolism, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Frizzled Receptors/metabolism, GTP-Binding Protein alpha Subunits, Gi-Go/metabolism, Immunohistochemistry, Oligonucleotides/genetics, Protein Transport, Signal Transduction/physiology, Wing/growth & development, Wnt Proteins/metabolism
Pubmed
Web of science
Create date
22/12/2011 16:12
Last modification date
20/08/2019 15:16
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