PUBLICATION

Beta-arrestin 2 regulates zebrafish development through the hedgehog signaling pathway

Authors
Wilbanks, A.M., Fralish, G.B., Kirby, M.L., Barak, L.S., Li, Y.X., and Caron, M.G.
ID
ZDB-PUB-041228-26
Date
2004
Source
Science (New York, N.Y.)   306(5705): 2264-2267 (Journal)
Registered Authors
Kirby, Margaret L.
Keywords
none
MeSH Terms
  • Animals
  • Arrestins/genetics
  • Arrestins/physiology*
  • Cell Differentiation
  • Cyclic AMP-Dependent Protein Kinases/genetics
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • In Situ Hybridization
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Muscle Cells/cytology
  • Muscle Fibers, Skeletal/cytology
  • Mutation
  • Phenotype
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/physiology
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism
  • Signal Transduction*
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
15618520 Full text @ Science
Abstract
beta-arrestins are multifunctional proteins that act as scaffolds and transducers of intracellular signals from heptahelical transmembrane-spanning receptors (7TMR). Hedgehog (Hh) signaling, which uses the putative 7TMR, Smoothened, is established as a fundamental pathway in development, and unregulated Hh signaling is associated with certain malignancies. Here, we show that the functional knockdown of beta-arrestin 2 in zebrafish embryos recapitulates the many phenotypes of Hh pathway mutants. Expression of wild-type beta-arrestin 2, or constitutive activation of the Hh pathway downstream of Smoothened, rescues the phenotypes caused by beta-arrestin 2 deficiency. These results suggest that a functional interaction between beta-arrestin 2 and Smoothened may be critical to regulate Hh signaling in zebrafish development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping