Personalized expression of bitter ‘taste’ receptors in human skin

Shaw, Lauren; Mansfield, Corrine; Colquitt, Lauren; Lin, Cailu; Ferreira, Jaime; Emmetsberger, Jaime; Reed, Danielle R.

doi:10.1371/journal.pone.0205322

Cited by 40 publications

(50 citation statements)

References 21 publications

(23 reference statements)

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“…Several other loci, such as that of TAS2R14 and TAS2R49, show an allele frequency difference of more than 10% between CRS patients and controls (92). Human skin expressed T2Rs, and the relative amounts differ markedly among individuals based on sun exposure, sex, and age (93).…”

Section: Figure 2 the Dynamic And Complex Interaction Between Risk Fmentioning

confidence: 99%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

233

184

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in which microRNAs (miRNAs) play a central role (Table 3). High-throughput profiling studies of well-characterized patients, including analyses of gene expression (e.g., microarrays and RNA sequencing transcriptomics), can help to identify combined signatures for type 2 and non-type 2 endotypes. They are enriching the available data for the identification of new potential targets. As critical components in the regulation of tissue homeostasis, miRNAs represent a very attractive field of precision medicine research in asthma and allergic diseases, as they have been linked to many biological mechanisms underlying Th2 cell and macrophage polarization, regulation of ILC2 biology, steroidresistant asthma phenotype, airway smooth muscle dysfunction, and impaired antiviral innate immunity (Table 3 and refs. 15-25). Thus, miRNAs represent a modifiable downstream target that will expand the precision medicine approach beyond the type 2/ non-type 2 paradigm. In one notable example of this approach, the use of gene expression microarrays on bronchial epithelial cells obtained from patients with asthma led to the identification of periostin, an IL-13-responsive biomarker (26-30). However, expression signatures are not highly specific for type 2 asthma: a recent study showed type 2 airway gene expression in a subset of patients with chronic obstructive pulmonary disease (COPD) (31).

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Section: Figure 2 the Dynamic And Complex Interaction Between Risk Fmentioning

confidence: 99%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

233

184

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“…OR gene expression has been established in a multitude of human tissues, that is, brain, blood leukocytes, airway smooth muscle, skin, gut [36,37,38,39,40,41,42,43,44,45]. Similarly, TAS1Rs and TAS2Rs are located in tissues other than the tongue and palate epithelium; including gastrointestinal tract, heart, leukocytes, vascular smooth muscle, airway epithelium, skin, lung and brain [39,46,47,48,49,50,51,52,53,54,55].…”

Section: “Ecnomotopic” Csgpcrs and Their Modulation By Small Molecmentioning

confidence: 99%

Beyond the Flavour: The Potential Druggability of Chemosensory G Protein-Coupled Receptors

Pizio

Behrens

Krautwurst

2019

IJMS

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G protein-coupled receptors (GPCRs) belong to the largest class of drug targets. Approximately half of the members of the human GPCR superfamily are chemosensory receptors, including odorant receptors (ORs), trace amine-associated receptors (TAARs), bitter taste receptors (TAS2Rs), sweet and umami taste receptors (TAS1Rs). Interestingly, these chemosensory GPCRs (csGPCRs) are expressed in several tissues of the body where they are supposed to play a role in biological functions other than chemosensation. Despite their abundance and physiological/pathological relevance, the druggability of csGPCRs has been suggested but not fully characterized. Here, we aim to explore the potential of targeting csGPCRs to treat diseases by reviewing the current knowledge of csGPCRs expressed throughout the body and by analysing the chemical space and the drug-likeness of flavour molecules.

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“…In recent years, transcripts of multiple bitter taste receptor (TAS2R) genes have been detected in human skin biopsies 17,18 . TAS2Rs are chemosensory G protein‐coupled receptors (GPCRs) employed by taste cells to recognize bitter‐tasting substances 19 .…”

Section: Introductionmentioning

confidence: 99%

Functionally expressed bitter taste receptor TAS2R14 in human epidermal keratinocytes serves as a chemosensory receptor

Bigliardi

Stelmashenko

et al. 2021

Experimental Dermatology

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Traditionally, it is theorized that skin sensation is initiated when cutaneous sensory afferents and Merkel cells receive sensory stimuli, while epidermal keratinocytes were deemed to have no role. However, mounting evidence has shown that keratinocytes can initiate skin sensation by receiving sensory stimuli and transmitting sensory information to sensory afferents. Knowledge regarding the mechanisms by which keratinocytes receive exogenous stimuli is limited, with TRP channels and olfactory receptors having been proposed to serve as receptors for exogenous stimuli in keratinocytes. Recently, expression analyses have demonstrated the expression of multiple TAS2R genes in human skin. TAS2Rs are chemosensory GPCRs employed by taste cells to detect bitter‐tasting substances. However, only subtypes TAS2R1 and TAS2R38 have been characterized in epidermal keratinocytes. We present evidence suggesting that subtype TAS2R14 is functionally expressed in epidermal keratinocytes. TAS2R14 transcripts and protein were detected in primary and N/TERT‐1 keratinocytes. Additionally, keratinocytes responded to α‐thujone, a TAS2R14 ligand, with an increase in intracellular free Ca2+ concentration. The tastant‐evoked Ca2+ signals were found to be mediated by wild‐type TAS2R14 and heterotrimeric G proteins. We conclude that TAS2R14 serves as a chemosensory receptor in epidermal keratinocytes and hypothesize that it enables the cells to recognize potentially harmful chemical substances.

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Personalized expression of bitter ‘taste’ receptors in human skin

Cited by 40 publications

References 21 publications

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Beyond the Flavour: The Potential Druggability of Chemosensory G Protein-Coupled Receptors

Functionally expressed bitter taste receptor TAS2R14 in human epidermal keratinocytes serves as a chemosensory receptor

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