Figure 1
The Hedgehog signalling pathway in Drosophila and vertebrates. (a) In Drosophila, Ptc inhibits Smo activity by suppressing the membrane stabilisation of Smo in the absence of Hh ligand. The Cos2, Ci, Fu and Sufu complex recruits kinases, such as PKA, CK1, Gsk3β, and promotes the cleavage of full-length Ci to become its repressor form (CiR) in a Slmb-dependent manner. Hh signalling transduction is blocked. (b) In Drosophila, Smo inhibition by Ptc is removed in the presence of Hh ligand. Smo is relocated to the plasma membrane and activated by several kinases, such as CK1, CK2, Gprk2 and PKA. The Fu-Cos2 complex is recruited to Smo and releases Ci. The released Ci is not cleaved and remains in its active form (CiA). CiA translocates into the nucleus and activates Hh downstream gene expression. (c) In vertebrates, Ptch1 is located in the cilium, whereas Smo is kept outside of cilium in the absence of Hh ligands. Gli is phosphorylated by kinases, such as PKA, CK1 and Gsk3β, which promote the processing of the repressor form (GliR) in a β-Trcp-dependent manner. Hh signalling is blocked. (d) In vertebrates, when Hh ligands bind to Ptch1, Smo inhibition is relieved. Ptch1 exits from the cilium, whereas Smo is translocated to cilium. The repressor form of the Gli (GliR), Sufu and Kif7 complex travels from the base of the cilium to the top via intraflagellar transport (IFT). Kif7 blocks the function of Sufu at the top of the cilium. Gli is not processed and ismaintained its active form (GliA). Activated Gli travels from the top of the cilium to the cytoplasm via IFT and translocates to the nucleus to transcript target genes thereby activating Hh signalling.
