title: 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 Ca(2+) 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.
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Scholz
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Mohrhardt
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Jansen
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kalbe
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haering
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Klasen
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum Bochum, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Osterloh
keywords: GPCR signal transduction; electrophysiology; olfactory pathways; olfactory receptor neurons; patch-clamp techniques