| First Author | Corbit KC | Year | 2005 |
| Journal | Nature | Volume | 437 |
| Issue | 7061 | Pages | 1018-21 |
| PubMed ID | 16136078 | Mgi Jnum | J:102118 |
| Mgi Id | MGI:3606828 | Doi | 10.1038/nature04117 |
| Citation | Corbit KC, et al. (2005) Vertebrate Smoothened functions at the primary cilium. Nature 437(7061):1018-21 |
| abstractText | 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. |
