Figure 1.

The outlines of Hh signaling

(A) In Drosophila, Ptc keeps Smo inactive, partly by promoting its internalization and degradation. Full-length Ci is sequestered in the cytoplasm in a complex with Cos2, Fu and Sufu, whereas Ci repressor (Ci^R) inhibits target gene expression in the nucleus. Hh blocks Ptc function, allowing the phosphorylation and dimerization/oligomerization of Smo, leading to Ci activation (Ci^A) and target gene expression. MT: microtubule;

(B) In vertebrates, Ptch1 in the primary cilia prevents Smo ciliary localization and activation. Gli3 enters the cilia with Sufu and Kif7 and is processed into Gli3^R. Shh binds Ptch1, leading to Smo ciliary translocation, phosphorylation, dimerization/oligomerization and Gli3 activation (Gli3^A). A membrane barrier near the base of the cilia prevents free diffusion of Smo.