Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment

Abstract Functional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in...

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Autores principales:	Elizabeth A. Corey, Sergei Zolotukhin, Barry W. Ache, Kirill Ukhanov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f523e7fe4c284db3aa43e4575a39ffc9
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spelling	oai:doaj.org-article:f523e7fe4c284db3aa43e4575a39ffc92021-12-02T17:39:32ZMixture interactions at mammalian olfactory receptors are dependent on the cellular environment10.1038/s41598-021-88601-02045-2322https://doaj.org/article/f523e7fe4c284db3aa43e4575a39ffc92021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88601-0https://doaj.org/toc/2045-2322Abstract Functional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in vitro in cell culture. The response dynamics and concentration-dependence of agonists for the ectopically expressed Olfr73 were similar to those reported for the endogenous Olfr73, however the antagonism previously reported between its cognate agonist and several antagonists was not replicated in vivo. Expressing the OR in vitro reproduced the antagonism reported for short odor pulses, but not for prolonged odor exposure. Our findings suggest that both the cellular environment and the stimulus dynamics shape the functionality of Olfr73 and argue that characterizing ORs in ‘native’ conditions, rather than in vitro, provides a more relevant understanding of ligand-OR interactions.Elizabeth A. CoreySergei ZolotukhinBarry W. AcheKirill UkhanovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth A. Corey Sergei Zolotukhin Barry W. Ache Kirill Ukhanov Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
description	Abstract Functional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in vitro in cell culture. The response dynamics and concentration-dependence of agonists for the ectopically expressed Olfr73 were similar to those reported for the endogenous Olfr73, however the antagonism previously reported between its cognate agonist and several antagonists was not replicated in vivo. Expressing the OR in vitro reproduced the antagonism reported for short odor pulses, but not for prolonged odor exposure. Our findings suggest that both the cellular environment and the stimulus dynamics shape the functionality of Olfr73 and argue that characterizing ORs in ‘native’ conditions, rather than in vitro, provides a more relevant understanding of ligand-OR interactions.
format	article
author	Elizabeth A. Corey Sergei Zolotukhin Barry W. Ache Kirill Ukhanov
author_facet	Elizabeth A. Corey Sergei Zolotukhin Barry W. Ache Kirill Ukhanov
author_sort	Elizabeth A. Corey
title	Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
title_short	Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
title_full	Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
title_fullStr	Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
title_full_unstemmed	Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
title_sort	mixture interactions at mammalian olfactory receptors are dependent on the cellular environment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f523e7fe4c284db3aa43e4575a39ffc9
work_keys_str_mv	AT elizabethacorey mixtureinteractionsatmammalianolfactoryreceptorsaredependentonthecellularenvironment AT sergeizolotukhin mixtureinteractionsatmammalianolfactoryreceptorsaredependentonthecellularenvironment AT barrywache mixtureinteractionsatmammalianolfactoryreceptorsaredependentonthecellularenvironment AT kirillukhanov mixtureinteractionsatmammalianolfactoryreceptorsaredependentonthecellularenvironment
_version_	1718379858481905664

Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment

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