Patched

Patched is part of a negative feedback mechanism for hedgehog signaling that helps shape the spatial gradient of signaling activity across tissues. In the absence of hedgehog, low levels of patched are sufficient to suppress activity of the signal transduction pathway. When hedgehog is present, its cholesterol moiety binds to the sterol-sensing domain in patched, which then inhibits the activity of smoothened. Smoothened is a G protein-coupled receptor, most of which is stored in membrane bound vesicles internally within the cell and which increases at the cell surface when hedgehog is present. Smoothened must be present on the cell membrane in order for the Hedgehog signaling pathway to be activated. Among other genes, the transcription of the patched gene is induced by hedgehog signaling, with the accumulation of the patched protein limiting signaling through the Smoothened protein. Recent work implicates the cilium in intracellular trafficking of hedgehog signaling components in vertebrate cells.

Mutated patched proteins have been implicated in a number of cancers including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma.^[3] Hereditary mutations in the human patched homolog PTCH1 cause autosomal dominant Gorlin syndrome, which consists of overgrowth and hereditary disposition to cancer including basal cell carcinoma and medulloblastoma. Mice with mutations in mouse PTCH1 similarly develop medulloblastoma.