Science · 2007 · 1.5K citations · 12 references
Life SciencesDevelopmental BiologyMolecular BiologyCell SignalingSignal TransductionStem Cell BiologyCancer Cell SignalingCancer Stem CellsDevelopmental Cell SignalingDevelopmental Signaling PathwaysHedgehog SignalingStem Cell Signaling PathwaysHedgehog Signal Transduction In DevelopmentHedgehog Signaling InhibitionPatched Receptor SignalingPrimary Cilium FunctionSignal Transduction In Hedgehog PathwaySignalsStem Cell Regulation By Hedgehog SignalingStem Function
Primary cilia are essential for transducing Hedgehog signaling in mammals. The study examined how primary cilia regulate the Hedgehog receptor Patched1. Binding of Shh to Patched1 causes the receptor to exit cilia, allowing Smoothened to accumulate and activate signaling. Patched1 resides in cilia and blocks Smoothened accumulation, and cilia‑mediated Hedgehog signaling is crucial for development, cancer, and stem cell biology.
Primary cilia are essential for transduction of the Hedgehog (Hh) signal in mammals. We investigated the role of primary cilia in regulation of Patched1 (Ptc1), the receptor for Sonic Hedgehog (Shh). Ptc1 localized to cilia and inhibited Smoothened (Smo) by preventing its accumulation within cilia. When Shh bound to Ptc1, Ptc1 left the cilia, leading to accumulation of Smo and activation of signaling. Thus, primary cilia sense Shh and transduce signals that play critical roles in development, carcinogenesis, and stem cell function.
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Vertebrate Smoothened functions at the primary cilium
Kevin C. Corbit, Pia Aanstad, Veena Singla et al. · Nature · 2005 · 1.5K citations
Hedgehog signalling in the mouse requires intraflagellar transport proteins
Danwei Huangfu, Aimin Liu, Andrew S. Rakeman et al. · Nature · 2003 · 1.4K citations
Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine
Jussi Taipale, James Chen, Michael K. Cooper et al. · Nature · 2000 · 1.3K citations
Small molecule modulation of Smoothened activity
James Chen, Jussi Taipale, Keith E. Young et al. · Proceedings of the National Academy of Sciences · 2002 · 996 citations