Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. elegans

Oosterveen, Tony, Coudreuse, Damien Y.M., Yang, Pei-Tzu, Fraser, Elizabeth, Bergsma, Joost, Dale, Trevor Clive ORCID: https://orcid.org/0000-0002-4880-9963 and Korswagen, Hendrik C. 2007. Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. elegans. Developmental Biology 308 (2) , pp. 438-448. 10.1016/j.ydbio.2007.05.043

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Abstract

Axin is a central component of the canonical Wnt signaling pathway that interacts with the adenomatous polyposis coli protein APC and the kinase GSK3β to downregulate the effector β-catenin. In the nematode Caenorhabditis elegans, canonical Wnt signaling is negatively regulated by the highly divergent Axin ortholog PRY-1. Mutation of pry-1 leads to constitutive activation of BAR-1/β-catenin-dependent Wnt signaling and results in a range of developmental defects. The pry-1 null phenotype is however not fully penetrant, indicating that additional factors may partially compensate for PRY-1 function. Here, we report the cloning and functional analysis of a second Axin-like protein, which we named AXL-1. We show that despite considerable sequence divergence with PRY-1 and other Axin family members, AXL-1 is a functional Axin ortholog. AXL-1 functions redundantly with PRY-1 in negatively regulating BAR-1/β-catenin signaling in the developing vulva and the Q neuroblast lineage. In addition, AXL-1 functions independently of PRY-1 in negatively regulating canonical Wnt signaling during excretory cell development. In contrast to vertebrate Axin and the related protein Conductin, AXL-1 and PRY-1 are not functionally equivalent. We conclude that Axin function in C. elegans is divided over two different Axin orthologs that have specific functions in negatively regulating canonical Wnt signaling.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
ISSN:	0012-1606
Funders:	Cancer Research UK
Date of Acceptance:	31 May 2007
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/61747

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