RGS proteins can regulate signaling from receptors that couple to heterotrimeric G proteins bearing an αi or αq subunit by acting as GTPase-activating proteins (GAPs). However, odorant receptors that act through an αs family member called αolf , which is insensitive to RGS, are also regulated by RGS proteins somehow. Sinnarajah et al. report that RGS2 blocks odorant-induced cAMP production in olfactory neurons by inhibiting adenylyl cylcase III. This inhibitory effect was independent of the effects of RGS2 on αs proteins in transfected cells. Presence of an RGS2-specific antibody also increased inward currents in response to stimulation of olfactory receptors in neurons. The authors propose that inhibition of adenylyl cyclase III by RGS2 may block the elevation of intracellular cAMP that is required to open cyclic nucleotide-gated channels. Thus, RGS proteins appear to regulate signaling through some G protein-coupled receptors by a mechanism other than GAP activity.
S. Sinnarajah, C.W. Dessauer, D. Srikumar, J. Chem, J. Yuen, S. Yilma, J.C. Dennis, E.E. Morrison, V. Vodyanoy, J.H. Kehrl, RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III. Nature 409, 1051-1055 (2001). [Online Journal]