| RRC ID |
3610
|
| Author |
Oosterveen T, Coudreuse DY, Yang PT, Fraser E, Bergsma J, Dale TC, Korswagen HC.
|
| Title |
Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. elegans.
|
| Journal |
Dev Biol
|
| 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.
|
| Volume |
308(2)
|
| Pages |
438-48
|
| Published |
2007-8-15
|
| DOI |
10.1016/j.ydbio.2007.05.043
|
| PII |
S0012-1606(07)01113-X
|
| PMID |
17601533
|
| MeSH |
Animals
Animals, Genetically Modified
Axin Protein
Base Sequence
Caenorhabditis elegans / genetics
Caenorhabditis elegans / growth & development
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
DNA, Helminth / genetics
Female
Genes, Helminth
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Signal Transduction
Vulva / growth & development
Vulva / metabolism
Wnt Proteins / genetics
Wnt Proteins / metabolism*
|
| IF |
2.896
|
| Times Cited |
17
|
|
WOS Category
|
DEVELOPMENTAL BIOLOGY
|
| Resource |
| C.elegans |
tm1095
tm1322
tm3122 |
