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

Abstract

BackgroundDomestic 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.ResultsWe 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.ConclusionsThese 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 materialThe online version of this article (doi:10.1186/s12868-015-0170-6) contains supplementary material, which is available to authorized users.

Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling

“…We have repeatedly found no effects of these DMSO levels on airway cell Ca 2ϩ or NO signaling (12,14,15,31,101,102), including here. Moreover, other studies have supported a specific role for T2R38 in AHL detection (103)(104)(105)(106) and also found no activation of endogenous T2R38 by 0.1% DMSO (107), as used here.…”

“…A recent study reported that T2R10 and T2R14, not T2R38, respond to some AHLs when expressed in HEK293 cells (46). The reason for this discrepancy is not yet clear, as other studies have shown that T2R38 detects AHLs (103)(104)(105)(106). We hypothesize that cloned receptor polymorphisms and/or different methodologies (microscopy versus plate reader assays) may contribute to some differential results observed.…”

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

“…Nevertheless, as the cat Tas2r38 ortholog shows insensitive PTC responsiveness and no PROP responses (72,73) we assumed the existence of a common ancestral TAS2R38 ortholog permissive for PTC/ PROP responses. Of course, the existence of further critical positions for PTC/PROP responses cannot be ruled out and may contribute significantly.…”

Receptor, signal transduction and evolution of sweet, umami and bitter taste

“…There are four to six T2R genes in fish and three in chickens, but 21-42 in mammals and 49 in frogs (Shi and Zhang 2006), indicating a species-or lineage-specific gene duplication event. In mammals, the evolutionary relationships of T2R gene families have been described in detail (Conte et al 2003;Fischer et al 2005;Go et al 2005;Lei et al 2015;Sandau et al 2015;Wang et al 2004). Five T2R protein groups existed prior to the divergence of the primate and rodent lineages (Conte et al 2003;Shi et al 2003), and the species-or lineage-specific gene duplication and pseudogenization were shown to play an important role in altering of the T2R gene repertoire in individual primate species (Go et al 2005;Zhao et al 2010).…”