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PMID:16136078
Citation |
Corbit, KC, Aanstad, P, Singla, V, Norman, AR, Stainier, DY and Reiter, JF (2005) Vertebrate Smoothened functions at the primary cilium. Nature 437:1018-21 |
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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. |
Links |
PubMed Online version:10.1038/nature04117 |
Keywords |
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 |
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