Patched1 regulates hedgehog signaling at the primary cilium.
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.
Rohatgi
Rajat
R
Departments of Developmental Biology, Genetics, and Bioengineering and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Milenkovic
Ljiljana
L
Scott
Matthew P
MP
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D003514:Cyclohexylamines / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000378:metabolism; D053823:Hedgehog Proteins / Q000819:agonists / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000494:pharmacology; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013876:Thiophenes / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
D003514:Cyclohexylamines; D053823:Hedgehog Proteins; D006888:Hydroxycholesterols; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C468918:SAG compound; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D013876:Thiophenes; C025813:20-hydroxycholesterol