Identification of a Novel Gnao-Mediated Alternate Olfactory Signaling Pathway in Murine OSNs

Abstract

It is generally agreed that in olfactory sensory neurons (OSNs), the binding of odorant molecules to their specific olfactory receptor (OR) triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG) channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG) and at least one other known weak Olfr73 agonist (Raspberry Ketone) trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell. Interestingly, this pathway is mediated by Gnao activation, leading to Cl− efflux; however, the activation of adenylyl cyclase III (ACIII), the recruitment of Ca2+ from extra-or intracellular stores, and phosphatidylinositol 3-kinase-dependent signaling (PI signaling) are not involved. Furthermore, we demonstrated that our newly identified pathway coexists with the canonical olfactory cAMP pathway in the same OSN and can be triggered by the same OR in a ligand-selective manner. We suggest that this pathway might reflect a mechanism for odor recognition predominantly used in early developmental stages before olfactory cAMP signaling is fully developed. Taken together, our findings support the existence of at least one odor-induced alternate signal transduction pathway in native OSNs mediated by Olfr73 in a ligand-selective manner.

Central role of G protein Gαi2 and Gαi2 + vomeronasal neurons in balancing territorial and infant-directed aggression of male mice

“…Omp is highly expressed in mature sensory neurons of MOE and VNO (46). Although Gαi2 is also expressed in some sensory neurons of the MOE (47), Gαi2 does not seem to participate in known sensory signaling events (48). Our conditional KO mice showed no obvious defects in MOE or MOB morphology and odor-guided behaviors depending on a functional MOE, indicating that the behavioral phenotypes we observe are largely mediated by VNO function.…”

Olfactory receptor OR2AT4 regulates human hair growth

“…When selected signaling pathways recognized to be involved in OR-mediated signaling 1 , 9 , 44 – 47 , were studied by phospho-kinase assay 9 , Sandalore ® upregulated several expected kinase activities (Fig. 7a and Table 1 ).…”

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

“…Moreover, the inhibitory G protein could also be a putative interaction partner of OR51E1 due to the finding that Gα i protein was weakly co-precipitated with OR51E1 protein. Recently, it was shown that beside Gα olf also Gα o is functionally coupled to ORs in olfactory sensory neurons [84]. …”