Functional and genomic comparative study of the bitter taste receptor family TAS2R: Insight into the role of human TAS2R5

Abstract

Bitterness is perceived in humans by 25 subtypes of bitter taste receptors (hTAS2R) that range from broadly tuned to more narrowly tuned receptors. hTAS2R5 is one of the most narrowly tuned bitter taste receptors in humans. In this study, we review the literature on this receptor and show there is no consensus about its role. We then compare the possible role of hTAS2R5 with that of the proteins of the TAS2R family in rat, mouse, and pig. A phylogenetic tree of all mammalian TAS2R domain‐containing proteins showed that human hTAS2R5 has no ortholog in pig, mouse, or rat genomes. By comparing the agonists that are common to hTAS2R5 and other members of the family, we observed that hTAS2R39 is the receptor that shares most agonists with hTAS2R5. In mouse, some of these agonists activate mTas2r105 and mTas2r144, which are distant paralogs of hTAS2R5. mTas2r144 seems to be the receptor that is most similar to hTAS2R5 because they are both activated by the same agonists and have affinities in the same range of values. Then, we can conclude that hTAS2R5 has a unique functional specificity in humans as it is activated by selective agonists and that its closest functional homolog in mouse is the phylogenetically distant mTas2r144.

Bitter taste receptors in the reproductive system: Function and therapeutic implications

“…For example, while a mouse has evolved 35 Tas2rs , humans have only 25 TAS2Rs . Some functional human TAS2Rs, such as TAS2R5, have no counterparts in mice, (Grau‐Bove et al, 2022) making it difficult to use mice as animal models to study these TAS2Rs. However, modern technologies can help overcome these challenges.…”

Bitter taste receptors along the gastrointestinal tract: comparison between humans and rodents

“…As their name suggests, their main role is to sense bitter components in food. This is a defence mechanism since, by sensing bitter, a food’s potentially toxic components can be detected ( 4 ) and their ingestion prevented, thus avoiding potential harmful effects. Not all bitter compounds are toxic, however, as they can also be found in high concentrations and with health benefits in foods of vegetal origin ( 3 , 4 , 12 ).…”

“…In humans, 25 functional genes and 11 pseudogenes encoded in chromosomes 5, 7 and 12 have been described ( 32–34 ). Mice have 36 functional receptors ( 4 ), which are encoded in chromosomes 2, 6, and 15 ( 33 ), and 6 pseudogenes ( 30 ). Rats possess 37 subtypes of bitter taste receptors ( 4 ), which are encoded in chromosomes 2, 3, and 4 ( 33 ) and possess 5 pseudogenes ( 30 ).…”

“…The answer could lie in their specific nature. Within this broad range of receptors, some are more specific and are activated by just a few ligands, while others are a target for many different compounds ( 4 , 35 ). At least in humans, TAS2Rs have been divided into four groups: (i) receptors that detect a broad spectrum of ligands, (ii) more selective receptors that detect just a few ligands, (iii) receptors that lie somewhere between these first two groups, and (iv) receptors that recognize specific chemical motifs ( 35 ).…”

“…This capability also facilitates recognition of beneficial or potentially harmful food components ( 2 , 3 ). The first step in taste sensing takes place within the oral cavity via the recognition of nutrients by specific receptors ( 2 , 4 ). However, some of these receptors have also been described in extraoral tissues such as the gastrointestinal tract, the respiratory system, and the reproductive organs ( 1 , 2 , 5 ).…”