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Science 317 (5836): 372-376

Copyright © 2007 by the American Association for the Advancement of Science

Patched1 Regulates Hedgehog Signaling at the Primary Cilium

Rajat Rohatgi,1,2* Ljiljana Milenkovic,1* Matthew P. Scott1{dagger}

Abstract: 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.

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.

{dagger} To whom correspondence should be addressed. E-mail: mscott{at}stanford.edu


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