Insect olfactory receptors are heteromeric ligand-gated ion channels

Nature. 2008 Apr 24;452(7190):1002-6. doi: 10.1038/nature06850. Epub 2008 Apr 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bombyx
  • Calcium / metabolism
  • Cell Line
  • Culicidae
  • Drosophila melanogaster
  • Electric Conductivity
  • HeLa Cells
  • Heterotrimeric GTP-Binding Proteins
  • Humans
  • Insecta / chemistry*
  • Ion Channel Gating*
  • Kinetics
  • Ligands
  • Odorants / analysis
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Receptors, Odorant / chemistry*
  • Receptors, Odorant / metabolism*
  • Smell
  • Xenopus laevis

Substances

  • Ligands
  • Protein Subunits
  • Receptors, Odorant
  • Heterotrimeric GTP-Binding Proteins
  • Calcium