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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arrestins / genetics
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Arrestins / physiology*
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Cell Differentiation
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Embryo, Nonmammalian / metabolism
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Gene Expression Regulation, Developmental
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Hedgehog Proteins
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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In Situ Hybridization
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Muscle Cells / cytology
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Muscle Fibers, Skeletal / cytology
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Mutation
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Patched Receptors
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Phenotype
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / physiology
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Signal Transduction*
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Smoothened Receptor
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Zebrafish / embryology*
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Zebrafish / genetics
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Zebrafish / metabolism*
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
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Zebrafish Proteins / physiology*
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beta-Arrestin 2
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beta-Arrestins
Substances
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ARRB2 protein, human
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Arrestins
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Hedgehog Proteins
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins
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Membrane Proteins
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Patched Receptors
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Repressor Proteins
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Smoothened Receptor
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Trans-Activators
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Transcription Factors
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Zebrafish Proteins
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beta-Arrestin 2
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beta-Arrestins
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smo protein, zebrafish
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Cyclic AMP-Dependent Protein Kinases