Figure 4 – Different ciliary environments facilitate specific signaling cascades.
A) Left: When peripheral energy stores are depleted, Leptin levels fall, leading Leptin-responsive neurons in the hypothalamus to make AgRP, an inverse agonist of MC4R. In the absence of MC4R activity, ADCY3 in neuronal cilia does not generate cAMP, spurring feeding. Right: When peripheral energy stores are repleted, Leptin triggers hypothalamic neurons to make αMSH, an MC4R agonist (green). Stimulating MC4R induces ADCY3 to generate ciliary cAMP, suppressing feeding. B) cAMP generated in the cilium activates a ciliary pool of PKA to turn off Hedgehog signal transduction.