Functional diversity of bitter taste receptor TAS2R16 in primates

Imai, Hiroo; Suzuki, Nami; Ishimaru, Yoshiro; Sakurai, Takanobu; Yin, Lijie; Pan, Wenbo; Abe, Keiko; Misaka, Takumi; Hirai, Hirohisa

doi:10.1098/rsbl.2011.1251

Cited by 42 publications

(40 citation statements)

References 15 publications

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“…Notably, the less responsive Asn172 is more common in individuals of African ancestry compared to those of European or Asian ancestry, the vast majority of whom carry the Lys172 allele. Similar small changes in TAS2R16 also explain differences in beta-glucopyranoside response across species (Imai, et al, 2012). …”

Section: Bitter Taste Differencesmentioning

confidence: 86%

Do polymorphisms in chemosensory genes matter for human ingestive behavior?

Hayes

Feeney

Allen

2013

Food Quality and Preference

147

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In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic differences restricted to bitterness. Perceptual variation has also been associated with polymorphisms in genes involved in odors associated with meat defects (boar taint), green/grassy notes, and cilantro, as well as umami and sweet tastes (TAS1R1/2/3). Here, a short primer on receptor genetics is provided, followed by a summary of current knowledge, and implications for human ingestive behavior are discussed.

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Section: Bitter Taste Differencesmentioning

confidence: 86%

Do polymorphisms in chemosensory genes matter for human ingestive behavior?

Hayes

Feeney

Allen

2013

Food Quality and Preference

147

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“…Humans have high sensitivity to most b-glucoside agonists [25]. Macaques have 10-fold lower sensitivity to b-glucoside agonists in comparison with humans [26]. This study showed that TAS2R16 responses to b-glucosides also vary among lemurs ( figure 1; electronic supplementary material, figure S2).…”

Section: Discussionmentioning

confidence: 63%

“…Furthermore, we identified the first natural inverse agonist of TAS2R16 and the key residues responsible for inverse agonist recognition by site-directed mutagenesis. Anthropoids, including humans, recognize b-glucosides via TAS2R16 [26]. We found that lemurs (strepsirrhines) also recognize b-glucosides via TAS2R16 (figure 1), indicating that b-glucoside-sensitive TAS2R16 was present in the last common ancestor of primates and is conserved in extant primates.…”

Section: Discussionmentioning

confidence: 76%

“…b-glucoside analogues, including many natural toxins, are molecules in which sugars are bound to other functional groups via b-glucosidic bonds and are specific agonists of TAS2R16 in humans [3,12,25]. The sensitivity of TAS2R16 to b-glucosides differs among catarrhine primates (human, apes and Old World monkeys) and TAS2R16 of a New World monkey, the common marmoset (Callithrix jacchus), does not respond to b-glucosides [26]. Mouse (Mus musculus), which is closely related to primates, recognizes b-glucosides via TAS2R41 (Tas2r126 in mouse nomenclature), not via TAS2R16 (Tas2r118) [4].…”

Section: Introductionmentioning

confidence: 99%

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A natural point mutation in the bitter taste receptor TAS2R16 causes inverse agonism of arbutin in lemur gustation

et al. 2019

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Bitter taste enables the detection of potentially harmful substances and is mediated by bitter taste receptors, TAS2Rs, in vertebrates. Few antagonists and inverse agonists of TAS2Rs have been identified, especially natural compounds. TAS2R16s in humans, apes and Old World monkeys (Catarrhini, Anthropoidea) recognize β-glucoside analogues as specific agonists. Here, we investigated responses of TAS2R16 to β-glucosides in non-anthropoid primates, namely lemurs (Lemuriformes, Strepsirrhini). Salicin acted as an agonist on lemur TAS2R16. Arbutin acted as an agonist in the ring-tailed lemur ( Lemur catta ) but as an inverse agonist in black lemur ( Eulemur macaco ) and black-and-white ruffed lemur ( Varecia variegata ). We identified a strepsirrhine-specific amino acid substitution responsible for the inverse agonism of arbutin. In a food preference test, salicin bitterness was inhibited by arbutin in the black lemur. Structural modelling revealed this locus was important for a rearrangement of the intracellular end of transmembrane helix 7 (TM7). Accordingly, arbutin is the first known natural inverse agonist of TAS2Rs, contributing to our understanding of receptor–ligand interactions and the molecular basis of the unique feeding habit diversification in lemurs. Furthermore, the identification of a causal point mutation suggests that TAS2R can acquire functional changes according to feeding habits and environmental conditions.

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“…Functional properties of the TAS2R38 receptor in colobines were evaluated using calcium imaging methods, as described previously [6,14,15]. To calculate responses to PTC, the amplitude of fluorescence was plotted against PTC concentration using IGOR Pro (WaveMetrics) and curves were fitted using nonlinear regression…”

Section: (D) Functional Assays Of Tas2r38mentioning

confidence: 99%

Functional characterization of the TAS2R38 bitter taste receptor for phenylthiocarbamide in colobine monkeys

et al. 2017

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Bitterness perception in mammals is mostly directed at natural toxins that induce innate avoidance behaviours. Bitter taste is mediated by the G protein-coupled receptor TAS2R, which is located in taste cell membranes. One of the best-studied bitter taste receptors is TAS2R38, which recognizes phenylthiocarbamide (PTC). Here we investigate the sensitivities of TAS2R38 receptors to PTC in four species of leaf-eating monkeys (subfamily Colobinae). Compared with macaque monkeys (subfamily Cercopithecinae), colobines have lower sensitivities to PTC in behavioural and in vitro functional analyses. We identified four non-synonymous mutations in colobine TAS2R38 that are responsible for the decreased sensitivity of the TAS2R38 receptor to PTC observed in colobines compared with macaques. These results suggest that tolerance to bitterness in colobines evolved from an ancestor that was sensitive to bitterness as an adaptation to eating leaves.

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Functional diversity of bitter taste receptor TAS2R16 in primates

Cited by 42 publications

References 15 publications

Do polymorphisms in chemosensory genes matter for human ingestive behavior?

Do polymorphisms in chemosensory genes matter for human ingestive behavior?

A natural point mutation in the bitter taste receptor TAS2R16 causes inverse agonism of arbutin in lemur gustation

Functional characterization of the TAS2R38 bitter taste receptor for phenylthiocarbamide in colobine monkeys

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