title: Functional architecture of olfactory ionotropic glutamate receptors.
abstract: Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here, we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed coreceptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into the use of IRs as genetically encoded chemical sensors.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Liliane
authors.initials: L
authors.lastname: Abuin
authors.forename: Benoîte
authors.initials: B
authors.lastname: Bargeton
authors.forename: Maximilian H
authors.initials: MH
authors.lastname: Ulbrich
authors.forename: Ehud Y
authors.initials: EY
authors.lastname: Isacoff
authors.forename: Stephan
authors.initials: S
authors.lastname: Kellenberger
authors.forename: Richard
authors.initials: R
authors.lastname: Benton
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000378:metabolism* / Q000502:physiology; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D058468:Receptors, Ionotropic Glutamate; D018035:Receptors, Odorant; C555767:ionotropic receptor 25a, Drosophila; C555766:ionotropic receptor 8a, Drosophila