Beta-arrestin 2 regulates zebrafish development through the hedgehog signaling pathway.
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.
Wilbanks
Alyson M
AM
Department of Cell Biology, Center for Models of Human Disease, Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC 27710, USA.
Fralish
Gregory B
GB
Kirby
Margaret L
ML
Barak
Larry S
LS
Li
Yin-Xiong
YX
Caron
Marc G
MG
D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009154:Mutation; D000072079:Patched Receptors; D010641:Phenotype; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D019390:Arrestins; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C491021:smo protein, zebrafish; D017868:Cyclic AMP-Dependent Protein Kinases