Dataset Information

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.

SUBMITTER: Scholz P

PROVIDER: S-EPMC4809895 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Scholz Paul P Mohrhardt Julia J Jansen Fabian F Kalbe Benjamin B Haering Claudia C Klasen Katharina K Hatt Hanns H Osterloh Sabrina S

Frontiers in cellular neuroscience 20160329

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 ...[more]

PMID: 27065801

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Project description:ccr encoding crotonyl coenzyme A (CoA) reductase (CCR), which catalyzes the conversion of crotonyl-CoA to butyryl-CoA in the presence of NADPH, was previously cloned from Streptomyces collinus. We now report that a complete open reading frame, designated meaA, is located downstream from ccr. The predicted gene product showed 35% identity with methylmalonyl-CoA mutases from various sources. In addition, the predicted amino acid sequences of S. collinus ccr and meaA exhibit strong similarity to that of adhA (43% identity), a putative alcohol dehydrogenase gene, and meaA (62% identity) of Methylobacterium extorquens, respectively. Both adhA and meaA are involved in the assimilation of C1 and C2 compounds in an unknown pathway in the isocitrate lyase (ICL)-negative Methylobacterium. We have demonstrated that S. collinus can grow with acetate as its sole carbon source even though there is no detectable ICL, suggesting that in this organism ccr and meaA may also be involved in a pathway for the assimilation of C2 compounds. Previous studies with streptomycetes provided a precedent for a pathway that initiates with the condensation of two acetyl-CoA molecules to form butyryl-CoA, which is then transformed to succinyl-CoA with two separate CoB12-mediated rearrangements and a series of oxidations. The biological functions of ccr and meaA in this process were investigated by gene disruption. A ccr-blocked mutant showed no detectable crotonyl-CoA reductase activity and, compared to the wild-type strain, exhibited dramatically reduced growth when acetate was the sole carbon source. An meaA-blocked mutant also exhibited reduced growth on acetate. However, both methylmalonyl-CoA mutase and isobutyryl-CoA mutase, which catalyze the two CoB12-dependent rearrangements in this proposed pathway, were shown to be present in the meaA-blocked mutant. These results suggested that both ccr and meaA are involved in a novel pathway for the growth of S. collinus when acetate is its sole carbon source.

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Dataset Information

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

Publications

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

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