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

Srikumar Sinnarajah, Carmen W. Dessauer, Deepa Srikumar, Jun Chen, John Yuen, Solomon Yilma, John C. Dennis, Edward E. Morrison, Vitaly Vodyanoy and John H. Kehrl ()
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Srikumar Sinnarajah: B cell Molecular Biology Section, Laboratory of Immunoregulation, NIAID, NIH
Carmen W. Dessauer: University of Texas-Houston Medical School
Deepa Srikumar: B cell Molecular Biology Section, Laboratory of Immunoregulation, NIAID, NIH
Jun Chen: University of Texas-Houston Medical School
John Yuen: B cell Molecular Biology Section, Laboratory of Immunoregulation, NIAID, NIH
Solomon Yilma: Physiology, and Pharmacology, Auburn University
John C. Dennis: Physiology, and Pharmacology, Auburn University
Edward E. Morrison: Physiology, and Pharmacology, Auburn University
Vitaly Vodyanoy: Physiology, and Pharmacology, Auburn University
John H. Kehrl: B cell Molecular Biology Section, Laboratory of Immunoregulation, NIAID, NIH

Nature, 2001, vol. 409, issue 6823, 1051-1055

Abstract: 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.

Date: 2001
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DOI: 10.1038/35059104

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