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 RIS Download
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