Role in Presence and Absence of Hedgehog Signaling
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 and binds to Patched, Patched somehow inhibits the activity of Smoothened, 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.
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