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
  • Immunoprecipitation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Animals
  • Cells, Cultured
  • Cytoskeletal Proteins/metabolism*
  • Humans
  • RNA Interference
  • Protein Binding
  • Receptors, LDL/metabolism*
  • Low Density Lipoprotein Receptor-Related Protein-6
  • In Situ Hybridization
  • Signal Transduction*
  • beta Catenin/metabolism*
  • Membrane Proteins/metabolism*
  • Repressor Proteins/metabolism*
  • DNA Primers
  • Base Sequence
  • Wnt Proteins/metabolism*
  • Axin Protein
(all 19)
PubMed
19572019 Full text @ PLoS One
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
Figures
Figure Gallery (2 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
frmd8MO1-frmd8MRPHLNO
frmd8MO2-frmd8MRPHLNO
1 - 2 of 2
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Fish
Fish
WT
1 - 1 of 1
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Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available
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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.