PUBLICATION
Bili inhibits Wnt/beta-catenin signaling by regulating the recruitment of axin to LRP6
- Authors
- Kategaya, L.S., Changkakoty, B., Biechele, T., Conrad, W.H., Kaykas, A., Dasgupta, R., and Moon, R.T.
- ID
- ZDB-PUB-090706-23
- Date
- 2009
- Source
- PLoS One 4(7): e6129 (Journal)
- Registered Authors
- Moon, Randall T.
- Keywords
- Small interfering RNAs, Wnt signaling cascade, Drosophila melanogaster, Embryos, Zebrafish, Luciferase, Membrane proteins, Genomic signal processing
- MeSH Terms
-
- Animals
- Axin Protein
- Base Sequence
- Cells, Cultured
- Cytoskeletal Proteins/metabolism*
- DNA Primers
- Humans
- Immunoprecipitation
- In Situ Hybridization
- Low Density Lipoprotein Receptor-Related Protein-6
- Membrane Proteins/metabolism*
- Protein Binding
- RNA Interference
- Receptors, LDL/metabolism*
- Repressor Proteins/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction*
- Wnt Proteins/metabolism*
- beta Catenin/metabolism*
- PubMed
- 19572019 Full text @ PLoS One
Citation
Kategaya, L.S., Changkakoty, B., Biechele, T., Conrad, W.H., Kaykas, A., Dasgupta, R., and Moon, R.T. (2009) Bili inhibits Wnt/beta-catenin signaling by regulating the recruitment of axin to LRP6. PLoS One. 4(7):e6129.
Abstract
BACKGROUND: Insights into how the Frizzled/LRP6 receptor complex receives, transduces and terminates Wnt signals will enhance our understanding of the control of the Wnt/ss-catenin pathway. METHODOLOGY/PRINCIPAL FINDINGS: In pursuit of such insights, we performed a genome-wide RNAi screen in Drosophila cells expressing an activated form of LRP6 and a beta-catenin-responsive reporter. This screen resulted in the identification of Bili, a Band4.1-domain containing protein, as a negative regulator of Wnt/beta-catenin signaling. We found that the expression of Bili in Drosophila embryos and larval imaginal discs significantly overlaps with the expression of Wingless (Wg), the Drosophila Wnt ortholog, which is consistent with a potential function for Bili in the Wg pathway. We then tested the functions of Bili in both invertebrate and vertebrate animal model systems. Loss-of-function studies in Drosophila and zebrafish embryos, as well as human cultured cells, demonstrate that Bili is an evolutionarily conserved antagonist of Wnt/beta-catenin signaling. Mechanistically, we found that Bili exerts its antagonistic effects by inhibiting the recruitment of AXIN to LRP6 required during pathway activation. CONCLUSIONS: These studies identify Bili as an evolutionarily conserved negative regulator of the Wnt/beta-catenin pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping