In vivo functions of the patched protein: Requirement of the C terminus for target gene inactivation but not hedgehog sequestration

The membrane protein Patched (Ptc) is a key regulator of Hedgehog (Hh) sign aling in development and is mutated in human tumors. Ptc opposes Hh-induced gene transcription and sequesters Hh protein. To dissect these functions, we tested partially deleted forms of Ptc in Drosophila. Deletion of either half of Ptc abolishes all function while coexpression of the halves restore s nearly full activity. Deletion of the final 156 residues of Ptc permits H h sequestration but abolishes inhibition of Hh targets. This deletion has d ominant-negative activity, promoting target gene activation in a ligand-ind ependent manner. We observe little or no association of full-length or part ially deleted Ptc with the membrane protein Smoothened in Drosophila cultur ed cells.