Figure 1.

Schematic diagram of the signal transduction mechanisms in mammals and insects. (A) Mammalian signaling and sites for regulation. Odorant ligand activates the odorant receptor (Or) that activates the G protein, G_olf. G_olf activates adenylyl cyclase type III (ACIII) that converts ATP to cAMP. cAMP opens cyclic nucleotide–gated (CNG) channels that allow sodium and calcium to enter the neuron. Calcium has a feed-forward effect by opening chloride channels that augment depolarization. Feedback mechanisms include PKA and GRK3 that phosphorylate activated receptors and facilitate the binding of β-arrestin 2 to block receptor/G_olf interactions. The calcium entering through the CNG channels binds calmodulin that activates the Ca²⁺-calmodulin dependent kinase II (CaMKII). CaMKII phosphorylates and inhibits the activity of ACIII and phosphorylates and activates the phosphodiesterase responsible for the hydrolysis of cAMP. (B) In insects, such as Drosophila, odorants activate the Or/Orco heterodimers leading to calcium influx. The elevated intracellular Ca²⁺ activates a phosphatase (or inhibits a kinase) resulting in gradual dephosphorylation of Orco^S289, resulting in desensitization of the olfactory receptors. ATP indicates adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Orco, odorant receptor coreceptor.