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  • Review Article
  • Published:

Genes and ligands for odorant, vomeronasal and taste receptors

Key Points

  • Chemosensation — the detection of chemicals in the external environment — is essential for the survival of the individual and of the species. The chemical senses (smell and taste) detect molecules of immense chemical variety, and this requires a massive array of receptors to match the diversity in chemical structures.

  • Olfactory signals are transduced by odorant receptors or ORs — a family of G-protein-coupled receptors (GPCRs). Axons of olfactory sensory neurons (OSNs) that express the same OR recognize each other and coalesce into discrete glomeruli in the olfactory bulb. The idea that each OSN expresses a single OR gene is widely accepted, but has not been proved.

  • Most mammals possess a second olfactory system — the accessory olfactory system or vomeronasal system. The mammalian vomeronasal organ (VNO) is generally considered to specialize in pheromone detection, although it does not have a monopoly in this regard. It also seems to detect 'common odorants' that are not typically regarded as pheromones. The vomeronasal receptors represent two superfamilies of GPCRs that are distinct from the OR superfamily.

  • The sensation of taste initiates at taste papillae that are distributed in and around the oral cavity. Each papilla contains one or more taste buds, each of which consists of around 100 cells, including taste receptor cells. Taste receptor genes, which code for another family of GPCRs, were the last mammalian chemosensory receptor genes to be identified.

  • Several assays have been developed to match odorants to ORs, and vice versa. The first unambiguous OR–ligand pair to be reported was the rat I7 receptor and octanal. This was identified using a system in which I7 was co-expressed with green fluorescent protein in OSNs. A heterologous expression system has also been developed in human embryonic kidney cells (HEK293), but its success has been limited, because expression of ORs on the cell surface is often poor.

  • For around 300 vomeronasal receptors in mice and rats, only one receptor–ligand interaction has been described to date. Seven T2R taste receptors have been functionally characterized, six in HEK293 heterologous expression systems and one by positional cloning in humans.

  • The identification of receptor–ligand interactions is not merely a descriptive exercise, but is directed towards understanding how chemical structure relates to chemosensory quality. For example, why does acetophenone smell like almond? This Holy Grail of olfaction is within sight, but there is still a long way to go.

Abstract

The chemical senses (smell and taste) have evolved complex repertoires of chemosensory receptors — G-protein coupled receptors with a seven-transmembrane domain structure. In the mouse, 1,000 odorant receptors are dedicated to the conventional sense of smell, 300 vomeronasal receptors mediate the detection of chemical stimuli (such as pheromones) by the vomeronasal organ, and 40 taste receptors are implicated in bitter, sweet and umami taste. Nearly all receptor genes have now been identified as the result of genome sequencing, but few receptor–ligand interactions have been characterized. Targeted expression of the green fluorescent protein in chemosensory cells is a promising approach to achieve this objective.

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Figure 1: The mammalian nose.
Figure 2: The mammalian tongue.
Figure 3: Odorant and vomeronasal receptors.
Figure 4: Wiring of the main olfactory and vomeronasal systems.
Figure 5: The odorant and vomeronasal receptor gene families.
Figure 6: Canonical pathway of signal transduction in olfactory sensory neurons.
Figure 7: Homologous in vivo assay for odorant responsiveness of odorant receptors.
Figure 8: Odorant response relationships.
Figure 9: The known non-chemosensory and chemosensory GPCR genes in mouse and human.

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Acknowledgements

I thank X. Zhang for producing figure 5a, T. Bozza for figure 8, and T. McClintock for useful comments.

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FURTHER INFORMATION

Encyclopedia of Life Sciences

chemosensory sytems

olfaction

pheromones in vertebrates

Glossary

G PROTEIN

A heterotrimeric GTP-binding and -hydrolysing protein that interacts with cell-surface receptors, often stimulating or inhibiting the activity of a downstream enzyme. G proteins consist of three subunits: the α-subunit, which contains the guanine-nucleotide-binding site; and the β- and γ-subunits, which function as a heterodimer.

DEGENERATE POLYMERASE CHAIN REACTION

PCR with primers that can anneal to various related sequences, some of which are unknown.

RT-PCR

Reverse transcriptase-polymerase chain reaction (PCR) — a reaction in which messenger RNA is converted into DNA (reverse transcription), which is then amplified by PCR.

IN SITU HYBRIDIZATION

A method that is used to label specific sequences of nucleic acids in cells or chromosomes. Commonly used to identify mRNA expression in tissue sections or whole mounts, this technique detects the formation of nucleic acid hybrid molecules between the target nucleic acid and a labelled probe that contains a complementary sequence.

POLYMORPHIC

A term that refers to genotypic variants that exist in the same population in frequencies that cannot be explained by recurrent mutations.

CDNA

Complementary DNA that is produced from an RNA template by an RNA-dependent DNA polymerase.

PSEUDOGENES

Genes that seem to be defective, due to the presence of features such as stop codons, frameshifts, internal deletions or an incomplete coding region.

MAJOR HISTOCOMPATIBILITY COMPLEX

(MHC). There are two classes of MHC molecules. MHC class I molecules are found on the surface of most cells and present proteins that are generated in the cytosol to T lymphocytes. MHC class II molecules are expressed only at the surface of activated antigen-presenting cells, and they present peptides that have been degraded in cellular vesicles to T cells.

ANOSMIC

Lacking the sense of smell.

GREEN FLUORESCENT PROTEIN

An autofluorescent protein that was originally isolated from the jellyfish Aequorea victoria. It can be genetically conjugated with proteins to make them fluorescent. The most widely used mutant, EGFP, has an emission maximum at 510 nm.

PATCH CLAMP

Technique whereby a small electrode tip is sealed onto a patch of cell membrane, making it possible to record the flow of current through individual ion channels or pores within the patch.

IRES

(Internal ribosome entry site). A sequence that is inserted between the coding regions for two proteins and allows efficient assembly of the ribosome complex in the middle of a transcript, leading to translation of the second protein.

QUANTITATIVE TRAIT LOCUS

A genetic locus or chromosomal region that contributes to variability in a complex quantitative trait (such as body weight), as identified by statistical analysis.

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Mombaerts, P. Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5, 263–278 (2004). https://doi.org/10.1038/nrn1365

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