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The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans.

Axin, APC, and the kinase GSK3 beta are part of a destruction complex that regulates the stability of the Wnt pathway effector beta-catenin. In C. elegans, several Wnt-controlled developmental processes have been described, but an Axin ortholog has not been found in the genome sequence and SGG-1/GSK3 beta, and the APC-related protein APR-1 have been shown to act in a positive, rather than negative fashion in Wnt signaling. We have shown previously that the EGL-20/Wnt-dependent expression of the homeobox gene mab-5 in the Q neuroblast lineage requires BAR-1/beta-catenin and POP-1/Tcf. Here, we have investigated how BAR-1 is regulated by the EGL-20 pathway. First, we have characterized a negative regulator of the EGL-20 pathway, pry-1. We show that pry-1 encodes an RGS and DIX domain-containing protein that is distantly related to Axin/Conductin. Our results demonstrate that despite its sequence divergence, PRY-1 is a functional Axin homolog. We show that PRY-1 interacts with BAR-1, SGG-1, and APR-1 and that overexpression of PRY-1 inhibits mab-5 expression. Furthermore, pry-1 rescues the zebrafish axin1 mutation masterblind, showing that it can functionally interact with vertebrate destruction complex components. Finally, we show that SGG-1, in addition to its positive regulatory role in early embryonic Wnt signaling, may function as a negative regulator of the EGL-20 pathway. We conclude that a highly divergent destruction complex consisting of PRY-1, SGG-1, and APR-1 regulates BAR-1/beta-catenin signaling in C. elegans.

Pubmed ID: 12023307

Authors

  • Korswagen HC
  • Coudreuse DY
  • Betist MC
  • van de Water S
  • Zivkovic D
  • Clevers HC

Journal

Genes & development

Publication Data

May 15, 2002

Associated Grants

None

Mesh Terms

  • Adenomatous Polyposis Coli Protein
  • Amino Acid Sequence
  • Animals
  • Axin Protein
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3
  • Glycoproteins
  • Green Fluorescent Proteins
  • Helminth Proteins
  • High Mobility Group Proteins
  • Hot Temperature
  • Insect Proteins
  • Luminescent Proteins
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Suppression, Genetic
  • Tissue Inhibitor of Metalloproteinase-3
  • Tissue Inhibitor of Metalloproteinases
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin