Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals

Neuron. 1998 Sep;21(3):495-504. doi: 10.1016/s0896-6273(00)80561-9.


Acute desensitization of olfactory signaling is a critical property of the olfactory system that allows animals to detect and respond to odorants. Correspondingly, an important feature of odorant-stimulated cAMP increases is their transient nature, a phenomenon that may be attributable to the unique regulatory properties of the olfactory adenylyl cyclase (AC3). AC3 is stimulated by receptor activation and inhibited by Ca2+ through Ca2+/calmodulin kinase II (CaMKII) phosphorylation at Ser-1076. Since odorant-stimulated cAMP increases are accompanied by elevated intracellular Ca2+, CaMKII inhibition of AC3 may contribute to termination of olfactory signaling. To test this hypothesis, we generated 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 phosphorylation was blocked by inhibitors of CaMKII, which also ablated cAMP decreases associated with odorant-stimulated cAMP transients. These data define a novel mechanism for termination of olfactory signaling that may be important in olfactory responses.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / chemistry
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Animals, Newborn
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cells, Cultured
  • Cilia / drug effects
  • Cilia / physiology
  • Cyclic AMP / metabolism
  • Enzyme Inhibitors / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / physiology*
  • Odorants*
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / physiology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Serine
  • Signal Transduction*


  • Adenylyl Cyclase Inhibitors
  • Enzyme Inhibitors
  • Peptide Fragments
  • Serine
  • Cyclic AMP
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Adenylyl Cyclases