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
Citation
Wilbanks, A.M., Fralish, G.B., Kirby, M.L., Barak, L.S., Li, Y.X., and Caron, M.G. (2004) Beta-arrestin 2 regulates zebrafish development through the hedgehog signaling pathway. Science (New York, N.Y.). 306(5705):2264-2267.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping