Identification of ligands for olfactory receptors by functional expression of a receptor library

Cell. 1998 Dec 23;95(7):917-26. doi: 10.1016/s0092-8674(00)81716-x.

Abstract

The recognition of odorants by olfactory receptors represents the first stage in odor discrimination. Here, we report the generation of an expression library containing a large and diverse repertoire of mouse olfactory receptor sequences in the transmembrane II-VII region. From this library, 80 chimeric receptors were tested against 26 odorants after transfection into HEK-293 cells. Three receptors were identified to respond to micromolecular concentrations of carvone, (-) citronellal, and limonene, respectively. We also found that the mouse I7 receptor, unlike the rat I7 receptor, prefers heptanal instead of octanal, as a result of a single valine-to-isoleucine substitution. This finding represents the beginning of a molecular understanding of odorant recognition. The identification, on a large scale, of cognate receptor-odorant interactions should provide insight into olfactory coding mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Acyclic Monoterpenes
  • Aldehydes / metabolism
  • Aldehydes / pharmacology
  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • Calcium Signaling
  • Cell Line
  • Cell Membrane / metabolism
  • Cloning, Molecular* / methods
  • Down-Regulation
  • Fatty Alcohols / metabolism
  • Fatty Alcohols / pharmacology
  • Isoproterenol / pharmacology
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Monoterpenes*
  • Peptide Library
  • Rats
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Odorant / chemistry
  • Receptors, Odorant / genetics*
  • Receptors, Odorant / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Terpenes / metabolism
  • Terpenes / pharmacology

Substances

  • Acyclic Monoterpenes
  • Aldehydes
  • Fatty Alcohols
  • Ligands
  • Monoterpenes
  • Peptide Library
  • Receptors, Adrenergic, beta
  • Receptors, Odorant
  • Recombinant Fusion Proteins
  • Terpenes
  • Rhodopsin
  • Isoproterenol
  • Acetylcholine
  • citronellal

Associated data

  • GENBANK/AF102516
  • GENBANK/AF102517
  • GENBANK/AF102518
  • GENBANK/AF102519
  • GENBANK/AF102520
  • GENBANK/AF102521
  • GENBANK/AF102522
  • GENBANK/AF102523
  • GENBANK/AF102524
  • GENBANK/AF102525
  • GENBANK/AF102526
  • GENBANK/AF102527
  • GENBANK/AF102528
  • GENBANK/AF102529
  • GENBANK/AF102530
  • GENBANK/AF102531
  • GENBANK/AF102532
  • GENBANK/AF102533
  • GENBANK/AF102534
  • GENBANK/AF102535
  • GENBANK/AF102536
  • GENBANK/AF102537
  • GENBANK/AF102538
  • GENBANK/AF102539
  • GENBANK/AF102540
  • GENBANK/AF102541
  • GENBANK/AF106007