Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 73, Issue 7, Pages 1317-1332Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-015-2127-4
Keywords
Smoothened; Patched; Gli; Signal transduction; PKA; Sufu; Crosstalk; GPCR; 7-DHC; Oxysterol; Primary cilium
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Funding
- French Centre National pour la Recherche Scientifique (CNRS)
- Association pour la Recherche contre le Cancer (ARC) [PJA 20131200185]
- Agence Nationale pour la Recherche, Programme Blanc
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The Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning and stem cell maintenance. In spite of intensive study, the mechanisms of Hh signal transduction are not completely understood. Here I review published data and present a novel model of vertebrate Hh signaling suggesting that Smoothened (Smo) functions as a G-protein-coupled receptor in cilia. This is the first model to propose molecular mechanisms for the major steps of Hh signaling, including inhibition of Smo by Patched, Smo activation, and signal transduction from active Smo to Gli transcription factors. It also suggests a novel role for the negative pathway regulators Sufu and PKA in these processes.
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