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

• Published in: Genes & development Vol. 16; no. 10; pp. 1291 - 1302
• Main Authors: Korswagen, Hendrik C, Coudreuse, Damien Y M, Betist, Marco C, van de Water, Sandra, Zivkovic, Danica, Clevers, Hans C
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15-05-2002
• Subjects: Adenomatous Polyposis Coli Protein - metabolism; Amino Acid Sequence; Animals; Axin Protein; beta Catenin; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Carrier Proteins - metabolism; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Developmental; Glycogen Synthase Kinase 3; Glycoproteins - genetics; Glycoproteins - metabolism; Green Fluorescent Proteins; Helminth Proteins - physiology; High Mobility Group Proteins - metabolism; Hot Temperature; Insect Proteins - metabolism; Luminescent Proteins - metabolism; Molecular Sequence Data; Mutation; Phenotype; Proteins - metabolism; Proto-Oncogene Proteins - physiology; Repressor Proteins; Research Paper; Sequence Homology, Amino Acid; Signal Transduction - physiology; Suppression, Genetic; Tissue Inhibitor of Metalloproteinase-3; Tissue Inhibitor of Metalloproteinases - metabolism; Trans-Activators; Wnt Proteins; Zebrafish Proteins
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.981802

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.