Practice question

Vertebrate Hedgehog signaling strictly requires primary cilium, solitary microtubule-based organelle protruding from most cells containing acetylated tubulin axoneme and basal body. Patched localizes near cilium base, upon Hedgehog binding exits cilium, Smoothened accumulates at ciliary membrane and transports Gli-Sufu complexes via intraflagellar transport proteins IFT88, IFT172, Kif3A, Kif7 to tip where phosphorylation by PKA, GSK3 changes convert Gli repressor to activator. Ciliary mutants lacking IFT display Hedgehog loss phenotype resembling Shh knockout, cyclopia, polydactyly despite normal receptors. Primary cilium acts as signaling hub compartmentalizing components facilitating proteolytic processing and activation, not degrading Patched.