Enhancement of transcription efficiency by TAR-Tat system increases the functional expression of human olfactory receptors

Humans have approximately 400 different olfactory receptors (hORs) and recognize odorants through the repertoire of hOR responses. Although the cell surface expression of hORs is critical to evaluate their response, hORs are poorly expressed on the surface of heterologous cells. To address this prob...

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Bibliographic Details
Published in:PloS one 2024-06, Vol.19 (6), p.e0306029
Main Authors: Ojiro, Ichie, Katsuyama, Hibiki, Kaneko, Ryusei, Ogasawara, Satoshi, Murata, Takeshi, Terada, Yuko, Ito, Keisuke
Format: Article
Language:English
Subjects:
Aldehydes - metabolism
Aldehydes - pharmacology
Aroma compounds
Cell surface
Chemosensory perception
Genes
Genetic transcription
Glucose
Hexanal
Humans
Inverse agonists
Odorant receptors
Odorants
Olfaction
Peptides
Positive feedback
Proteins
Reagents
Receptors
Receptors, Odorant - genetics
Receptors, Odorant - metabolism
Scientific equipment and supplies industry
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Transcription, Genetic
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Summary:Humans have approximately 400 different olfactory receptors (hORs) and recognize odorants through the repertoire of hOR responses. Although the cell surface expression of hORs is critical to evaluate their response, hORs are poorly expressed on the surface of heterologous cells. To address this problem, previous studies have focused on hOR transportation to the membrane. Nevertheless, the response pattern of hORs to odorants has yet to be successfully linked, and the response sensitivity still remains to be improved. In this study, we demonstrate that increasing the transcriptional level can result in a significant increase in cell surface and functional expression of hORs. We used the TAR-Tat system, which increases the transcription efficiency through positive feedback, and found that OR1A1, OR6N2, and OR51M1 exhibited robust expression. Moreover, this system induces enhanced hOR responses to odorants, thus defining four hORs as novel n-hexanal receptors and n-hexanal is an inverse agonist to one of them. Our results suggested that using the TAR-Tat system and increasing the transcriptional level of hORs can help understanding the relationship between hORs and odorants that were previously undetectable. This finding could facilitate the understanding of the sense of smell by decoding the repertoire of hOR responses.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0306029