Therapeutic potential of ectopic olfactory and taste receptors

Abstract

Olfactory and taste receptors are expressed primarily in the nasal olfactory epithelium and gustatory taste bud cells, where they transmit real-time sensory signals to the brain. However, they are also expressed in multiple extra-nasal and extra-oral tissues, being implicated in diverse biological processes including sperm chemotaxis, muscle regeneration, bronchoconstriction and bronchodilatation, inflammation, appetite regulation and energy metabolism. Elucidation of the physiological roles of these ectopic receptors is revealing potential therapeutic and diagnostic applications in conditions including wounds, hair loss, asthma, obesity and cancers. This Review outlines current understanding of the diverse functions of ectopic olfactory and taste receptors and assesses their potential to be therapeutically exploited.

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Fig. 1: Major signalling pathways and functions regulated by ectopic olfactory receptors.
Fig. 2: Activation of ectopic olfactory receptors regulates cancer cell growth.
Fig. 3: Pathways activated by ectopic taste receptors in the gut and adipose tissue.
Fig. 4: Antibacterial effects of ectopic taste receptors in the lung.

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Acknowledgements

The authors thank C. Wu and Y.-J. Kim for assistance in manuscript preparations. This work was supported by a grant from the National Research Foundation (NRF) of Korea (NRF-2018R1A4A1022589 and 2016R1A2A2A05005483), funded by the South Korean government (MSIP), and was supported by a grant from the University of Leuven (Methusalem grant) and Research Foundation Flanders (G073615N).

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Glossary

Olfactory receptors

(ORs). A type of membrane receptor expressed in the cilia of the olfactory sensory neurons, where they bind to odorants to give the sensation of smell. ORs are also expressed in diverse extra-nasal tissues and are involved in diverse biological functions.

Taste receptors

A type of receptor that binds to tastants dissolved in saliva to facilitate the sensation of taste. Taste receptors are widely expressed in diverse tissues and play multiple biological roles.

Sperm chemotaxis

A form of sperm guidance in which spermatozoa follow a concentration gradient of a chemoattractant secreted from the oocyte and thereby reach the oocyte.

Adipogenesis

The process of cell differentiation by which pre-adipocytes become adipocytes.

Keratinocytes

Cells that are a major component of the epidermis, the outer layer of the skin, which synthesizes keratin. Keratinocytes are involved in the intricate mechanisms of initiation, maintenance and completion of wound healing.

Orthologue

A homologous gene that is related to those in different organisms by descent from the DNA of a common ancestor.

Pseudogenes

Sequences of DNA resembling a gene but usually containing mutations that alter or abolish gene function; pseudogenes thus cannot produce a normal protein.

Gustducin and transducin

Specific types of G protein expressed in the gustatory system and extra-oral tissues that interact with G protein-coupled receptors that act as sweet, umami and bitter taste receptors. Gustducin and transducin are structurally and functionally similar and interact with taste receptors to generate diverse signal transduction pathways.

Negative chronotropic and inotropic effects

Negative inotropic effects reduce cardiac contractility, while negative chronotropic effects lower the rate of heartbeat.

Transcriptome

A collection of all the mRNA expressed in a biological sample such as a cell or tissue.

Hyperventilation

Abnormal fast and deep breathing; the result of either an emotional status or a physiological condition such as asthma.

Chemokinesis

An increased nondirectional activity of cells owing to the presence of chemical substances; this is opposed to the oriented movement of chemotaxis.

Myogenesis

The formation of muscle fibres from primordial muscle cells known as myoblasts.

RNA-sequencing

(RNA-seq). A powerful technique used to profile the transcriptome of biological samples to examine the presence and quality of mRNA.

Melanogenesis

The production of melanin from the amino acid tyrosine via complex metabolic pathways; the process is carried out by melanocytes located in the bottom layer of the skin epidermis.

Next-generation sequencing

A high-speed nucleic acid sequencing technique, typically characterized by being highly scalable, allowing the entire genome to be sequenced at once.

Gut hormones

A group of hormones (for example, ghrelin, glucagon-like peptide 1 (GLP1) and cholecystokinin (CCK)) secreted by enteroendocrine cells in the gastrointestinal tract that regulate several biological functions involved in the regulation of food intake, digestion, motility and so on.

Beige adipocyte

Under certain circumstances (such as prolonged cold exposure), a ‘beiging’ process occurs in white adipocytes resulting in the formation of beige adipocytes, which function similarly to brown adipocytes and produce heat by activation of oxidative metabolism.

Innate immune response

The component of the immune system that is nonspecific, as distinguished from the adaptive immune response. It provides the first line of defence against pathogens.

Bronchodilatation

A widening of the lumen of the bronchi, allowing increased airflow to and from the lungs.

Rhinosinusitis

Inflammation of the sinuses resulting in clinical symptoms of thick nasal mucus, a plugged nose and pain in the face.

Nucleic acid aptamers

Oligonucleotides (single-stranded DNAs or RNAs) that bind to a specific target molecule with high affinity and specificity. Aptamers can target proteins that remain inaccessible to antibodies and could be functional in a wider range of conditions.

Protein scaffolds

Small proteins designed to bind to a specific target molecule with high affinity and specificity. These scaffolds can target proteins that remain inaccessible to antibodies and could be functional in a wider range of conditions.

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Lee, S., Depoortere, I. & Hatt, H. Therapeutic potential of ectopic olfactory and taste receptors. Nat Rev Drug Discov 18, 116–138 (2019). https://doi.org/10.1038/s41573-018-0002-3

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