RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III

Nature. 2001 Feb 22;409(6823):1051-5. doi: 10.1038/35059104.


The heterotrimeric G-protein Gs couples cell-surface receptors to the activation of adenylyl cyclases and cyclic AMP production (reviewed in refs 1, 2). RGS proteins, which act as GTPase-activating proteins (GAPs) for the G-protein alpha-subunits alpha(i) and alpha(q), lack such activity for alpha(s) (refs 3-6). But several RGS proteins inhibit cAMP production by Gs-linked receptors. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the alpha(s) family member alpha(olf) links odorant receptors to adenylyl cyclase activation. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on alpha(olf) but by inhibiting the activity of adenylyl cyclase type III, the predominant adenylyl cyclase isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively regulates odorant-evoked intracellular signalling. These results reveal a mechanism for controlling the activities of adenylyl cyclases, which probably contributes to the ability of olfactory neurons to discriminate odours.

Publication types

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

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Cell Line
  • Cell Membrane / enzymology
  • Cell Membrane / metabolism
  • Cyclic AMP / metabolism
  • Enzyme Activation
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Olfactory Receptor Neurons / metabolism*
  • Patch-Clamp Techniques
  • RGS Proteins / physiology*
  • Rats
  • Recombinant Proteins
  • Signal Transduction*
  • Transfection


  • Adenylyl Cyclase Inhibitors
  • Isoenzymes
  • RGS Proteins
  • Recombinant Proteins
  • Rgs2 protein, mouse
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Cyclic AMP
  • Adenylyl Cyclases
  • adenylate cyclase 3