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.
Bibliographical noteFunding Information:
We are especially grateful to Dr Philipp Roland Kaldis (Lund University, Sweden) for his invaluable advice and support. We thank Dr Graham Wright (Research Support Center, Agency for Science, Technology and Research, Singapore) for his technical assistance in the rescue experiments, and Dr Maik Behrens for his generous gift of pcDNA5/FRT-SSTR3-TAS2R14-HSV. We also thank the two anonymous reviewers for their comments which helped to improve this manuscript.
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
- G protein-coupled receptors
- calcium signaling
PubMed: MeSH publication types
- Journal Article