The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans (original) (raw)
- Hendrik C. Korswagen1,3,4,
- Damien Y.M. Coudreuse1,3,
- Marco C. Betist1,
- Sandra van de Water1,
- Danica Zivkovic1, and
- Hans C. Clevers2
- 1Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands;2Department of Immunology and Center for Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
Abstract
Axin, APC, and the kinase GSK3β are part of a destruction complex that regulates the stability of the Wnt pathway effector β-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/GSK3β, 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/β-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/β-catenin signaling in C. elegans.
Footnotes
↵3 These authors contributed equally to this work.
↵4 Corresponding author.
E-MAIL rkors{at}niob.knaw.nl; FAX 31-30-251-6464.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.981802.
- Received February 4, 2002.
- Accepted April 8, 2002.
Cold Spring Harbor Laboratory Press