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A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs

BACKGROUND: Domestic cats (felis catus) have a reputation for being rather unpredictable in their dietary choices. While their appetite for protein or savory flavors is consistent with their nutritional needs, their preference among protein-sufficient dietary options may relate to differences in the...

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Autores principales: Sandau, Michelle M, Goodman, Jason R, Thomas, Anu, Rucker, Joseph B, Rawson, Nancy E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453034/
https://www.ncbi.nlm.nih.gov/pubmed/26037485
http://dx.doi.org/10.1186/s12868-015-0170-6
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author Sandau, Michelle M
Goodman, Jason R
Thomas, Anu
Rucker, Joseph B
Rawson, Nancy E
author_facet Sandau, Michelle M
Goodman, Jason R
Thomas, Anu
Rucker, Joseph B
Rawson, Nancy E
author_sort Sandau, Michelle M
collection PubMed
description BACKGROUND: Domestic cats (felis catus) have a reputation for being rather unpredictable in their dietary choices. While their appetite for protein or savory flavors is consistent with their nutritional needs, their preference among protein-sufficient dietary options may relate to differences in the response to other flavor characteristics. Studies of domestic cat taste perception are limited, in part, due to the lack of receptor sequence information. Several studies have described the phylogenetic relationship of specific cat taste receptor sequences as compared with other carnivores. For example, domestic cats are obligate carnivores and their receptor Tas1r2, associated with the human perception of sweet, is present only as a pseudogene. Similarly, the cat perception of bitter may differ from that of other mammals due to variations in their repertoire of bitter receptor (Tas2r) genes. This report includes the first functional characterization of domestic cat taste receptors. RESULTS: We functionally expressed two uncharacterized domestic sequences Tas2r38 and Tas2r43 and deorphanized the receptors using a cellular functional assay. Statistical significance was determined using an unpaired, two-tailed t-test. The cat sequence for Tas2r38 contains 3 major amino acid residues known to confer the taster phenotype (PAI), which is associated with sensitivity to the bitter compounds PROP and PTC. However, in contrast to human TAS2R38, cat Tas2r38 is activated by PTC but not by PROP. Furthermore, like its human counterpart, cat Tas2r43 is activated by aloin and denatonium, but differs from the human TAS2R43 by insensitivity to saccharin. The responses of both cat receptors to the bitter ligands were concentration-dependent and were inhibited by the human bitter blocker probenecid. CONCLUSIONS: These data demonstrate that the response profiles of the cat bitter receptors Tas2r38 and Tas2r43 are distinct from those of their orthologous human receptors. Results with cat Tas2r38 also demonstrate that additional residues beyond those classically associated with PROP sensitivity in humans influence the sensitivity to PROP and PTC. Functional studies of the human bitter receptor family are being applied to the development of food and medicinal products with more appealing flavor profiles. Our work lays the foundation for similar work applied to felines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-015-0170-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-44530342015-06-04 A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs Sandau, Michelle M Goodman, Jason R Thomas, Anu Rucker, Joseph B Rawson, Nancy E BMC Neurosci Research Article BACKGROUND: Domestic cats (felis catus) have a reputation for being rather unpredictable in their dietary choices. While their appetite for protein or savory flavors is consistent with their nutritional needs, their preference among protein-sufficient dietary options may relate to differences in the response to other flavor characteristics. Studies of domestic cat taste perception are limited, in part, due to the lack of receptor sequence information. Several studies have described the phylogenetic relationship of specific cat taste receptor sequences as compared with other carnivores. For example, domestic cats are obligate carnivores and their receptor Tas1r2, associated with the human perception of sweet, is present only as a pseudogene. Similarly, the cat perception of bitter may differ from that of other mammals due to variations in their repertoire of bitter receptor (Tas2r) genes. This report includes the first functional characterization of domestic cat taste receptors. RESULTS: We functionally expressed two uncharacterized domestic sequences Tas2r38 and Tas2r43 and deorphanized the receptors using a cellular functional assay. Statistical significance was determined using an unpaired, two-tailed t-test. The cat sequence for Tas2r38 contains 3 major amino acid residues known to confer the taster phenotype (PAI), which is associated with sensitivity to the bitter compounds PROP and PTC. However, in contrast to human TAS2R38, cat Tas2r38 is activated by PTC but not by PROP. Furthermore, like its human counterpart, cat Tas2r43 is activated by aloin and denatonium, but differs from the human TAS2R43 by insensitivity to saccharin. The responses of both cat receptors to the bitter ligands were concentration-dependent and were inhibited by the human bitter blocker probenecid. CONCLUSIONS: These data demonstrate that the response profiles of the cat bitter receptors Tas2r38 and Tas2r43 are distinct from those of their orthologous human receptors. Results with cat Tas2r38 also demonstrate that additional residues beyond those classically associated with PROP sensitivity in humans influence the sensitivity to PROP and PTC. Functional studies of the human bitter receptor family are being applied to the development of food and medicinal products with more appealing flavor profiles. Our work lays the foundation for similar work applied to felines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-015-0170-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-03 /pmc/articles/PMC4453034/ /pubmed/26037485 http://dx.doi.org/10.1186/s12868-015-0170-6 Text en © Sandau et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sandau, Michelle M
Goodman, Jason R
Thomas, Anu
Rucker, Joseph B
Rawson, Nancy E
A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs
title A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs
title_full A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs
title_fullStr A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs
title_full_unstemmed A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs
title_short A functional comparison of the domestic cat bitter receptors Tas2r38 and Tas2r43 with their human orthologs
title_sort functional comparison of the domestic cat bitter receptors tas2r38 and tas2r43 with their human orthologs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453034/
https://www.ncbi.nlm.nih.gov/pubmed/26037485
http://dx.doi.org/10.1186/s12868-015-0170-6
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