title: Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. elegans.
abstract: Axin is a central component of the canonical Wnt signaling pathway that interacts with the adenomatous polyposis coli protein APC and the kinase GSK3beta to downregulate the effector beta-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/beta-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/beta-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.
authors.affiliation: Hubrecht Institute, Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
authors.forename: Tony
authors.initials: T
authors.lastname: Oosterveen
authors.forename: Damien Y M
authors.initials: DY
authors.lastname: Coudreuse
authors.forename: Pei-Tzu
authors.initials: PT
authors.lastname: Yang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fraser
authors.forename: Joost
authors.initials: J
authors.lastname: Bergsma
authors.forename: Trevor C
authors.initials: TC
authors.lastname: Dale
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Korswagen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D060466:Axin Protein; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018509:DNA, Helminth / Q000235:genetics; D005260:Female; D017238:Genes, Helminth; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014844:Vulva / Q000254:growth & development / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060466:Axin Protein; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D018509:DNA, Helminth; C117260:Pry-1 protein, C elegans; D012097:Repressor Proteins; D051153:Wnt Proteins; C115014:bar-1 protein, C elegans; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3