Publication Date:
2004-12-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilbanks, Alyson M -- Fralish, Gregory B -- Kirby, Margaret L -- Barak, Larry S -- Li, Yin-Xiong -- Caron, Marc G -- GM069086-01/GM/NIGMS NIH HHS/ -- HL36059/HL/NHLBI NIH HHS/ -- HL61365/HL/NHLBI NIH HHS/ -- NS19576/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 24;306(5705):2264-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Center for Models of Human Disease, Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15618520" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Arrestins/genetics/*physiology
;
Cell Differentiation
;
Cyclic AMP-Dependent Protein Kinases/genetics/metabolism
;
Embryo, Nonmammalian/metabolism
;
Gene Expression Regulation, Developmental
;
Hedgehog Proteins
;
Homeodomain Proteins/genetics/metabolism
;
In Situ Hybridization
;
Membrane Proteins/genetics/metabolism
;
Muscle Cells/cytology
;
Muscle Fibers, Skeletal/cytology
;
Mutation
;
Phenotype
;
Receptors, Cell Surface
;
Receptors, G-Protein-Coupled/genetics/physiology
;
Repressor Proteins/genetics/metabolism
;
*Signal Transduction
;
Trans-Activators/genetics/*metabolism
;
Transcription Factors/genetics/metabolism
;
Zebrafish/*embryology/genetics/*metabolism
;
Zebrafish Proteins/genetics/metabolism/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
