Dual roles for patched in sequestering and transducing Hedgehog.
Secreted proteins of the Hedgehog (Hh) family have diverse organizing roles in animal development. Recently, a serpentine protein Smoothened (Smo) has been proposed as a Hh receptor. Here, we present evidence that implicates another multiple-pass transmembrane protein, Patched (Ptc), in Hh reception and suggests a novel signal transduction mechanism in which Hh binds to Ptc, or a Ptc-Smo complex, and thereby induces Smo activity. Our results also show that Ptc limits the range of Hh action; we provide evidence that high levels of Ptc induced by Hh serve to sequester any free Hh and therefore create a barrier to its further movement.
Howard Hughes Medical Institute, Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
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Struhl
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D007301:Insect Hormones / Q000235:genetics / Q000502:physiology*; D019476:Insect Proteins / Q000502:physiology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D005810:Multigene Family; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor; D014921:Wings, Animal / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D007301:Insect Hormones; D019476:Insect Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C064196:dpp protein, Drosophila; C070844:ptc protein, Drosophila; C100664:smo protein, Drosophila; C077245:hh protein, Drosophila