title: Three structurally similar odorants trigger distinct signaling pathways in a mouse olfactory neuron.
abstract: In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor gene. By calcium imaging of individual OSNs in intact mouse olfactory turbinates, we observed that a subset of OSNs (Ho-OSNs) located in the most ventral olfactory receptor zone can mediate distinct signaling pathways when activated by structurally similar ligands. Calcium imaging showed that Ho-OSNs were highly sensitive to 2-heptanone, heptaldehyde and cis-4-heptenal. 2-heptanone-evoked intracellular calcium elevation was mediated by cAMP signaling while heptaldehyde triggered the diacylglycerol pathway. An increase of intracellular calcium evoked by cis-4-heptenal was due to a combination of activation mediated by the adenylate cyclase pathway and suppression generated by phospholipase C signaling. Pharmacological studies demonstrated that novel mechanisms were involved in the phospholipase C-mediated intracellular calcium changes. Binary-mixture studies and cross-adaptation data indicate that three odorants acted on the same olfactory receptor. The feature that an olfactory receptor mediates multiple signaling pathways was specific for Ho-OSNs and not established in another population of OSNs characterized. Our study suggests that distinct signaling pathways triggered by ligand-induced conformational changes of an olfactory receptor constitute a complex information process mechanism in olfactory transduction. This study has important implications beyond olfaction in that it provides insights of plasticity and complexity of G-protein-coupled receptor activation and signal transduction.
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn Street, Chicago, IL 60616, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Boyer
authors.affiliation: Department of Biological and Chemical Sciences, Illinois Institute of Technology, 3101 S. Dearborn Street, Chicago, IL 60616, USA. Electronic address: ZhangC@iit.edu.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D051379:Mice; D009812:Odorants; D009833:Olfactory Pathways / Q000187:drug effects* / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012903:Smell / Q000187:drug effects / Q000502:physiology
chemical_list: D007659:Ketones; C011917:2-heptanone; D002118:Calcium
keywords: adenylate cyclase; calcium imaging; olfactory neuron; olfactory receptor; phospholipase C; sensory transduction