Differential role of Axin RGS domain function in Wnt signaling during anteroposterior patterning and maternal axis formation

Patricia N Schneider; Diane C Slusarski; Douglas W Houston

doi:10.1371/journal.pone.0044096

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Differential role of Axin RGS domain function in Wnt signaling during anteroposterior patterning and maternal axis formation

Journal article

Open access

Peer reviewed

Differential role of Axin RGS domain function in Wnt signaling during anteroposterior patterning and maternal axis formation

Patricia N Schneider, Diane C Slusarski and Douglas W Houston

PloS one, Vol.7(9), pp.e44096-e44096

2012

DOI: 10.1371/journal.pone.0044096

PMCID: PMC3434218

PMID: 22957046

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Abstract

Axin is a critical component of the β-catenin destruction complex and is also necessary for Wnt signaling initiation at the level of co-receptor activation. Axin contains an RGS domain, which is similar to that of proteins that accelerate the GTPase activity of heterotrimeric Gα/Gna proteins and thereby limit the duration of active G-protein signaling. Although G-proteins are increasingly recognized as essential components of Wnt signaling, it has been unclear whether this domain of Axin might function in G-protein regulation. This study was performed to test the hypothesis that Axin RGS-Gna interactions would be required to attenuate Wnt signaling. We tested these ideas using an axin1 genetic mutant (masterblind) and antisense oligo knockdowns in developing zebrafish and Xenopus embryos. We generated a point mutation that is predicted to reduce Axin-Gna interaction and tested for the ability of the mutant forms to rescue Axin loss-of-function function. This Axin point mutation was deficient in binding to Gna proteins in vitro, and was unable to relocalize to the plasma membrane upon Gna overexpression. We found that the Axin point mutant construct failed to rescue normal anteroposterior neural patterning in masterblind mutant zebrafish, suggesting a requirement for G-protein interactions in this context. We also found that the same mutant was able to rescue deficiencies in maternal axin1 loss-of-function in Xenopus. These data suggest that maternal and zygotic Wnt signaling may differ in the extent of Axin regulation of G-protein signaling. We further report that expression of a membrane-localized Axin construct is sufficient to inhibit Wnt/β-catenin signaling and to promote Axin protein turnover.

Protein Structure, Tertiary

Signal Transduction

Xenopus laevis

Frizzled Receptors - metabolism

Zebrafish

Structure-Activity Relationship

RNA, Messenger - metabolism

Wnt Proteins - metabolism

beta Catenin - metabolism

Axin Protein - metabolism

Point Mutation

Phenotype

Animals

Gene Expression Regulation, Developmental

Models, Biological

Body Patterning

Mutation

GTP-Binding Proteins - metabolism

Details

Title: Subtitle: Differential role of Axin RGS domain function in Wnt signaling during anteroposterior patterning and maternal axis formation
Creators: Patricia N Schneider - Interdisciplinary Graduate Program in Genetics, Department of Biology, University of Iowa, Iowa City, Iowa, United States of America
Diane C Slusarski
Douglas W Houston
Resource Type: Journal article
Publication Details: PloS one, Vol.7(9), pp.e44096-e44096
DOI: 10.1371/journal.pone.0044096
PMID: 22957046
PMCID: PMC3434218
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: R01 GM083999 / NIGMS NIH HHS R01 CA112369 / NCI NIH HHS
Language: English
Date published: 2012
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9983991979002771

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