title: Insect olfactory receptors are heteromeric ligand-gated ion channels.
abstract: In insects, each olfactory sensory neuron expresses between one and three ligand-binding members of the olfactory receptor (OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor. The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant-binding subunit and one constant Or83b family subunit. Insect ORs lack homology to G-protein-coupled chemosensory receptors in vertebrates and possess a distinct seven-transmembrane topology with the amino terminus located intracellularly. Here we provide evidence that heteromeric insect ORs comprise a new class of ligand-activated non-selective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca2+ influx and cation-non-selective ion conductance on stimulation with odorant. Odour-evoked OR currents are independent of known G-protein-coupled second messenger pathways. The fast response kinetics and OR-subunit-dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant-gated channels was obtained by outside-out patch-clamp recording of Xenopus oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand-gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.
authors.affiliation: Department of Integrated Biosciences, The University of Tokyo, Chiba 277-8562, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellegrino
authors.forename: Takao
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Vosshall
authors.forename: Kazushige
authors.initials: K
authors.lastname: Touhara
mesh_terms: D000818:Animals; D012831:Bombyx; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D009033:Culicidae; D004331:Drosophila melanogaster; D004553:Electric Conductivity; D006367:HeLa Cells; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D007313:Insecta / Q000737:chemistry*; D015640:Ion Channel Gating; D007700:Kinetics; D008024:Ligands; D009812:Odorants / Q000032:analysis; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D018035:Receptors, Odorant / Q000737:chemistry* / Q000378:metabolism*; D012903:Smell; D014982:Xenopus laevis
chemical_list: D008024:Ligands; D021122:Protein Subunits; D018035:Receptors, Odorant; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium