Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. elegans.
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.
Oosterveen
Tony
T
Hubrecht Institute, Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Coudreuse
Damien Y M
DY
Yang
Pei-Tzu
PT
Fraser
Elizabeth
E
Bergsma
Joost
J
Dale
Trevor C
TC
Korswagen
Hendrik C
HC
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*
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