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Patched1 Regulates Hedgehog Signaling at the Primary Cilium
Rajat Rohatgi,1,2*Ljiljana Milenkovic,1*Matthew P. Scott1
Primary cilia are essential for transduction of the Hedgehog(Hh) signal in mammals. We investigated the role of primarycilia in regulation of Patched1 (Ptc1), the receptor for SonicHedgehog (Shh). Ptc1 localized to cilia and inhibited Smoothened(Smo) by preventing its accumulation within cilia. When Shhbound to Ptc1, Ptc1 left the cilia, leading to accumulationof Smo and activation of signaling. Thus, primary cilia senseShh and transduce signals that play critical roles in development,carcinogenesis, and stem cell function.
1 Departments of Developmental Biology, Genetics, and Bioengineering and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. 2 Department of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: mscott{at}stanford.edu
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