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

机译:家猫苦味受体Tas2r38和Tas2r43与人类直系同源物的功能比较

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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.
机译:背景技术家猫(felis catus)的饮食选择难以预测。虽然它们对蛋白质或咸味的食欲与其营养需求相一致,但它们在蛋白质充足的饮食选择中的偏爱可能与对其他风味特征的反应差异有关。对家猫的味觉知觉的研究有限,部分是由于缺乏受体序列信息。一些研究已经描述了与其他食肉动物相比特定猫味受体序列的系统发育关系。例如,家猫是专性食肉动物,它们与人类对甜味的感知相关的受体Tas1r2仅作为假基因存在。同样,由于猫的苦味受体(Tas2r)基因组成不同,猫对苦味的感觉可能与其他哺乳动物不同。该报告包括家猫味觉受体的第一个功能表征。结果我们使用细胞功能测定法功能性表达了两个未表征的国内序列Tas2r38和Tas2r43,并对受体进行了脱孤。使用不成对的两尾t检验确定统计学显着性。 Tas2r38的cat序列包含3个主要氨基酸残基,已知这些氨基酸残基赋予了味觉表型(PAI),这与对苦味化合物PROP和PTC的敏感性有关。但是,与人TAS2R38相比,猫Tas2r38是由PTC激活的,而不是由PROP激活的。此外,与其人类对应物一样,猫Tas2r43也被芦荟素和地那铵激活,但与人TAS2R43的区别在于对糖精不敏感。两种猫受体对苦味配体的反应均是浓度依赖性的,并被人类苦味阻断剂丙磺舒抑制。结论这些数据表明,猫苦味受体Tas2r38和Tas2r43的应答谱不同于其直系同源人类受体的应答谱。猫Tas2r38的结果还表明,除了人类经典与PROP敏感性相关的那些残基外,其他残基也会影响对PROP和PTC的敏感性。人类苦味受体家族的功能研究被用于开发具有更吸引人的风味的食品和药品。我们的工作为应用于猫科动物的类似工作奠定了基础。

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