Vertebrate Smoothened functions at the primary cilium

@article{Corbit2005VertebrateSF,
  title={Vertebrate Smoothened functions at the primary cilium},
  author={Kevin C. Corbit and Pia Aanstad and Veena Singla and Andrew R. Norman and Didier Y. R. Stainier and Jeremy F. Reiter},
  journal={Nature},
  year={2005},
  volume={437},
  pages={1018-1021}
}
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… Expand
The primary cilium as a Hedgehog signal transduction machine.
TLDR
The evidence that defines the integral roles that IFT proteins and cilia play in the regulation of the Hh signal transduction pathway in vertebrates is reviewed, and the mechanisms that control localization of Hh pathway proteins to the cilium are discussed. Expand
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TLDR
The data suggest that the Smo-Evc2 signaling complex at the EvC zone is required for Hh signal transmission and elucidate the molecular basis of two human ciliopathies. Expand
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TLDR
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TLDR
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TLDR
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The graded response to Sonic Hedgehog depends on cilia architecture.
TLDR
A mouse mutation is described that causes coupled defects in cilia structure and Sonic hedgehog (Shh) signaling, and normal structure of the ciliary axoneme is required for the cell to translate different levels of Shh ligand into differential regulation of the Gli transcription factors that implement Hedgehog signals. Expand
Cilia-mediated hedgehog signaling in Drosophila.
TLDR
It is shown that Cos2 and Fused are required for the ciliary transport of Smoothened and that cilia mediate the expression of the Hh pathway target genes, and that the cilia HH pathway is conserved from Drosophila to vertebrates. Expand
Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
TLDR
It is shown that ciliary localization of Sufu is dependent on ciliary-localized Gli proteins, and is inhibited by PKA activation, suggesting a coordinated mechanism for the ciliary translocation of Su Fu and Gliprotein. Expand
Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis
TLDR
The screen for compounds that alter the ciliary localization of YFP-tagged Smo identified 10 compounds that inhibit Hh pathway activity, and reveals that different pools of Smo move into cilia through distinct mechanisms. Expand
Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus
TLDR
Changes in ciliary and nuclear trafficking of Gli2 are triggered by the Hh-dependent accumulation of activated Smo in the cilium, resulting in a shift from primarily cytoplasmic localization to accumulation at the distal tip of thecilium and within the nucleus. Expand
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