PHOSPHORYLATION AND INHIBITION OF OLFACTORY ADENYLYL-CYCLASE BY CAM KINASE-II IN NEURONS - A MECHANISM FOR ATTENUATION OF OLFACTORY SIGNALS

Acute desensitization of olfactory signaling is a critical property of the olfactory system that allows animals to detect and respond to odo rants. Correspondingly, an important feature of odorant-stimulated cAM P increases is their transient nature, a phenomenon that may be attrib utable to the unique regulatory properties of the olfactory adenylyl c yclase (AC3). AC3 is stimulated by receptor activation and inhibited b y Ca2+ through Ca2+/calmodulin kinase II(CaMKII) phosphorylation at Se r-1076. Since odorant-stimulated cAMP increases are accompanied by ele vated intracellular Ca2+, CaMKII inhibition of AC3 may contribute to t ermination of olfactory signaling. To test this hypothesis, we generat ed a polyclonal antibody specific for AC3 phosphorylated at Ser-1076. A brief exposure of mouse olfactory cilia or primary olfactory neurons to odorants stimulated phosphorylation of AC3 at Ser-1076. This phosp horylation was blocked by inhibitors of CaMKII, which also ablated cAM P decreases associated with odorant-stimulated cAMP transients. These data define a novel mechanism for termination of olfactory signaling t hat may be important in olfactory responses.