Hedgehog pathway overview. In vertebrates, the response of cells to Hh ligands is coordinated at the primary cilium (PC), a finger-like projection on the cell surface. (a) In the absence of ligand, the Hh receptor Patched localizes to the PC, keeping membrane targeted Smoothened out and in an inactive state. In the absence of Smoothened activity, Protein Kinase A (PKA) localized at the base of the PC promotes the cleavage of the Gli transcription factor into a repressor form that enters the nucleus and represses target gene expression. (b) On binding to Hh, Patched is internalized and targeted to the lysosome. Released from its Patched-mediated inhibition, Smoothened moves into the primary cilium where its activity attenuates the PKA-dependent cleavage of the Gli transcription factors, allowing their full-length forms to enter the cilium. Here they are activated by Smoothened before moving to the nucleus to activate target gene transcription.
Carney and Ingham BMC Biology 2013 11:37 doi:10.1186/1741-7007-11-37