PUBLICATION
Vertebrate Smoothened functions at the primary cilium
- Authors
- Corbit, K.C., Aanstad, P., Singla, V., Norman, A.R., Stainier, D.Y., and Reiter, J.F.
- ID
- ZDB-PUB-050907-11
- Date
- 2005
- Source
- Nature 437(7061): 1018-1021 (Journal)
- Registered Authors
- Aanstad, Pia, Norman, Andrew, Reiter, Jeremy, Stainier, Didier
- Keywords
- none
- MeSH Terms
-
- Amino Acid Motifs
- Amino Acid Sequence
- Animals
- Caenorhabditis elegans/chemistry
- Cell Line
- Cilia/drug effects
- Cilia/metabolism*
- Dogs
- Drosophila Proteins/chemistry
- Embryo, Mammalian/metabolism
- Embryo, Nonmammalian
- Genes, Reporter/genetics
- Mice
- Mutation/genetics
- Protein Sorting Signals/genetics
- Protein Sorting Signals/physiology
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Receptors, G-Protein-Coupled/antagonists & inhibitors
- Receptors, G-Protein-Coupled/chemistry
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism*
- Signal Transduction
- Veratrum Alkaloids/pharmacology
- Vertebrates/embryology
- Vertebrates/genetics
- Vertebrates/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 16136078 Full text @ Nature
Citation
Corbit, K.C., Aanstad, P., Singla, V., Norman, A.R., Stainier, D.Y., and Reiter, J.F. (2005) Vertebrate Smoothened functions at the primary cilium. Nature. 437(7061):1018-1021.
Abstract
The unanticipated involvement of several intraflagellar transport proteins in the mammalian Hedgehog (Hh) pathway has hinted at a functional connection between cilia and Hh signal transduction. Here we show that mammalian Smoothened (Smo), a seven-transmembrane protein essential for Hh signalling, is expressed on the primary cilium. This ciliary expression is regulated by Hh pathway activity; Sonic hedgehog or activating mutations in Smo promote ciliary localization, whereas the Smo antagonist cyclopamine inhibits ciliary localization. The translocation of Smo to primary cilia depends upon a conserved hydrophobic and basic residue sequence homologous to a domain previously shown to be required for the ciliary localization of seven-transmembrane proteins in Caenorhabditis elegans. Mutation of this domain not only prevents ciliary localization but also eliminates Smo activity both in cultured cells and in zebrafish embryos. Thus, Hh-dependent translocation to cilia is essential for Smo activity, suggesting that Smo acts at the primary cilium.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping