Abstract
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 α-subunits αi and αq, lack such activity for αs (refs 3,4,5,6). But several RGS proteins inhibit cAMP production by Gs-linked receptors7,8. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the αs family member αolf links odorant receptors to adenylyl cyclase activation9,10. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on αolf 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.
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Acknowledgements
We thank M. Rust for editorial assistance; K. Druey, H. Cho and A. Sheschonka for the recombinant RGS proteins; and A. Fauci for support. E.M. and V.V. were supported by grants from the Office of Special Technology, Federal Aviation Administration and Defense Advanced Research Project Agency. C.W.D. was supported by the American Heart Association and the National Institutes of Health.
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Sinnarajah, S., Dessauer, C., Srikumar, D. et al. RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III. Nature 409, 1051–1055 (2001). https://doi.org/10.1038/35059104
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DOI: https://doi.org/10.1038/35059104
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