2005
DOI: 10.1038/nature04117
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Vertebrate Smoothened functions at the primary cilium

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 inhi… Show more

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Cited by 1,339 publications
(1,334 citation statements)
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“…For example, in the mouse, cilia may be used to amplify signals downstream of Shh (Huangfu et al, 2003;Corbit et al, 2005;Liu et al, 2005).…”
Section: Do Cilia Initiate or Transmit Lr Information?mentioning
confidence: 99%
“…For example, in the mouse, cilia may be used to amplify signals downstream of Shh (Huangfu et al, 2003;Corbit et al, 2005;Liu et al, 2005).…”
Section: Do Cilia Initiate or Transmit Lr Information?mentioning
confidence: 99%
“…3 signalling by binding to the Ptch1 receptor and inducing subsequent internalisation and lysosomal degradation of the Hh-Ptch complex (Incardona et al, 2000), thereby allowing translocation of Smo to the tip of the primary cilium where it is phosphorylated into an active form (Corbit et al, 2005) (Rohatgi et al, 2007). Ptch1 itself is a transcriptional target of the pathway, a feedback mechanism that acts to increase the amount of Ptch1 protein available to further bind and deplete Hh ligand from the microenvironment.…”
Section: A C C E P T E D Accepted Manuscriptmentioning
confidence: 99%
“…Smo, a seven-pass transmembrane protein of the extended G-protein-coupled receptor family, has an active and an inactivate state that appears to be defined both by its location within the cell (inside or outside of the primary cilia) [31] and by other modifications that may include its ability to capture oxysterols at an active site [32,33]. Smo activation requires two steps that were operationally defined by certain low-molecular-weight compounds that disrupt the activation process [34].…”
Section: Overview Of the Hedgehog Signaling Pathwaymentioning
confidence: 99%