RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III.
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.
Sinnarajah
S
S
Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland 20892, USA.
Dessauer
C W
CW
Srikumar
D
D
Chen
J
J
Yuen
J
J
Yilma
S
S
Dennis
J C
JC
Morrison
E E
EE
Vodyanoy
V
V
Kehrl
J H
JH
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020710:RGS Proteins / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins; D015398:Signal Transduction; D014162:Transfection
D000067956:Adenylyl Cyclase Inhibitors; D007527:Isoenzymes; D020710:RGS Proteins; D011994:Recombinant Proteins; C105345:Rgs2 protein, mouse; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3