Taste receptor

Savory or glutamates (Umami)

The TAS1R1+TAS1R3 heterodimer receptor functions as an umami receptor, responding to L-amino acid binding, especially L-glutamate.^[14] The umami taste is most frequently associated with the food additive monosodium glutamate (MSG) and can be enhanced through the binding of inosine monophosphate (IMP) and guanosine monophosphate (GMP) molecules.^[15][16] TAS1R1+3 expressing cells are found mostly in the fungiform papillae at the tip and edges of the tongue and palate taste receptor cells in the roof of the mouth.^[14] These cells are shown to synapse upon the chorda tympani nerves to send their signals to the brain, although some activation of the glossopharyngeal nerve has been found.^[15][17]

Alternative candidate umami taste receptors include splice variants of metabotropic glutamate receptors, mGluR4 and mGluR1, and the NMDA receptor.^{[11][18][19][20]}

Not all animals use T1R1+T1R3 as the umami receptor; shifts in what a receptor detects often happen with evolution.^[21] For examples, sweet-sensing songbirds have repurposed their umami receptor into a sweet receptor.^[22]

Almost every major vertebrate lineage uses a TAS1R to detect amino acids, a signal of the nutritional quality of food. However, glutamate is not among the more commonly-detected amino acids; instead, early vertebrates may have focused on basic and branched-chain amino acids, as this was the shared preference among bichir and elephant shark, representative of the bony and cartilaginous fishes respectively.^[21]

Sweet

The TAS1R2+TAS1R3 heterodimer receptor functions as the sweet receptor by binding to a wide variety of sugars and sugar substitutes.^[14][23][24] TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth.^[14] These cells are shown to synapse upon the chorda tympani and glossopharyngeal nerves to send their signals to the brain.^[11][17]

Sensing of the sweet taste has changed throughout the evolution of different animals. The T1R2/T1R3 setup is used by mammals and lizards. In birds, however, the T1R2 gene family does not exist and they sense the sweet taste through T1R1/T1R3 (the umami receptor in mammals). In teleost fish, neither T1R1/T1R3 or T1R2/T1R3 detect sweetness (sucrose). In the bichir, T1R1/T1R3 detects both sucralose and amino acids, and T1R2/T1R3 only detects amino acids.^[21] The bird T1R1/T1R3 underwent a process of repurposing: along the evolution stages of sweet-sensing songbirds, there was a decrease in its ability to sense the umami taste, and an increase in the ability to sense the sweet taste. The primordial songbird T1R1/T1R3 would have only tasted umami. This shift corresponded with a change in the structure of the ligand binding site.^[22]

Bitter

The TAS2R proteins (InterPro: IPR007960) function as bitter taste receptors.^[25] There are 43 human TAS2R genes, each of which (excluding the five pseudogenes) lacks introns and codes for a GPCR protein.^[11] These proteins, as opposed to TAS1R proteins, have short extracellular domains and are located in circumvallate papillae, palate, foliate papillae, and epiglottis taste buds, with reduced expression in fungiform papillae.^[4][11] Though it is certain that multiple TAS2Rs are expressed in one taste receptor cell, it is still debated whether mammals can distinguish between the tastes of different bitter ligands.^[4][11] Some overlap must occur, however, as there are far more bitter compounds than there are TAS2R genes. In silico modelling results suggest that bitterness receptors tend to cluster into three distinct groups based on their interaction with bitter ligands relevant to wine.^[26] Common bitter ligands include cycloheximide, denatonium, PROP (6-n-propyl-2-thiouracil), PTC (phenylthiocarbamide), and β-glucopyranosides.^[11]

Signal transduction of bitter stimuli is accomplished via the α-subunit of gustducin. This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the transduction pathway are still unknown. The βγ-subunit of gustducin also mediates taste by activating IP₃ (inositol triphosphate) and DAG (diglyceride). These second messengers may open gated ion channels or may cause release of internal calcium.^[27] Though all TAS2Rs are located in gustducin-containing cells, knockout of gustducin does not completely abolish sensitivity to bitter compounds, suggesting a redundant mechanism for bitter tasting^[13] (unsurprising given that a bitter taste generally signals the presence of a toxin).^[13] One proposed mechanism for gustducin-independent bitter tasting is via ion channel interaction by specific bitter ligands, similar to the ion channel interaction which occurs in the tasting of sour and salty stimuli.^[11]

One of the best-researched TAS2R proteins is TAS2R38, which contributes to the tasting of both PROP and PTC. It is the first taste receptor whose polymorphisms are shown to be responsible for differences in taste perception. Current studies are focused on determining other such taste phenotype-determining polymorphisms.^[11] More recent studies show that genetic polymorphisms in other bitter taste receptor genes influence bitter taste perception of caffeine, quinine and denatonium benzoate.^[28]

It has been demonstrated that bitterness receptors (TAS2R) play an important role in an innate immune system of airway (nose and sinuses) ciliated epithelium tissues.^[29] This innate immune system adds an "active fortress"^[30] to the physical Immune system surface barrier. This fixed immune system is activated by the binding of ligands to specific receptors. These natural ligands are bacterial markers, for TAS2R38 example: acyl-homoserine lactones^[31] or quinolones^[32] produced by Pseudomonas aeruginosa. To defend against predators, some plants have produced mimic bacterial markers substances. These plant mimes are interpreted by the tongue, and the brain, as being bitterness. The fixed immune system receptors are identical to the bitter taste receptors, TAS2R. Bitterness substances are agonist of TAS2R fixed immune system. ^[29] The innate immune system uses nitric oxide and defensins which are capable of destroying bacteria, and also viruses.^[33][34] These fixed innate immune systems (Active Fortresses) are known in other epithelial tissues than upper airway (nose, sinuses, trachea, bronchi), for example: breast (mammary epithelial cells), gut and also human skin (keratinocytes)^[35] Bitter molecules, their associated bitter taste receptors, and the sequences and homology models of bitter taste receptors, are available via BitterDB.

Not through taste receptors

These tastes are not mediated by the standard "taste receptors". A brief description of their molecular bases follows.

Sour

Main article: Taste § Sourness

Historically it was thought that the sour taste was produced solely when free hydrogen ions (H⁺) directly depolarised taste receptors. However, specific receptors for sour taste with other methods of action are now being proposed. The HCN channels were such a proposal; as they are cyclic nucleotide-gated channels. The two ion channels now suggested to contribute to sour taste are ASIC2 and TASK-1. OTOP1 is also thought to be a sour taste receptor.^{[36][37][38][39]}

Loss of function

The TAS1R (T1R) genes have seen shifts in their functions in many lineages, occasionally amounting to the complete loss of a gene. These appetitive receptors decide what an animal likes. There is a correlation between inactivation of T1R genes and feeding behavior.^[55]

The T1R2/T1R3 taste receptor complex detects sweetness in mammals and lizards – presumably the ancestral state of tetrapods.^[56] Many Carnivoran mammals are unable to detect sweetness in food, including cats and vampire bats, due to the pseudogenization of T1R2. This pseudogenization is quite widespread in the order, having occurred independently in several lineages via different mutations to the same gene. This is an example of convergent evolution.^[56] Furthermore, pseudogenization of T1R2 are also known in chickens and the Western clawed frog.^[56]

The T1R1/T1R3 taste receptor complex detects umami in mammals.^[56] In two lineages of aquatic mammals including dolphins and sea lions, Tas1r1 has been found to be pseudogenized.^[56] The pseudogenization of Tas1r1 has also been found in terrestrial, carnivorous species.^[56] While the panda belongs to the order Carnivora, it is herbivorous where 99% of its diet is bamboo, and it cannot taste umami.^[57] Genome sequence of the panda shows that its Tas1r1 gene is pseudogenized.^[57] In a study, it was found that in all species in the order Carnivora except the panda, the open reading frame was maintained.^[57] In panda, the nonsynonymous to synonymous substitutions ratio was found to be much higher than other species in order Carnivora.^[57] This data correlates with fossil records date of the panda to show where panda switched from carnivore to herbivore diet.^[56] Therefore, the loss of function of umami in panda is hypothesized to be caused by dietary change where the panda became less dependence on meat.^[56] However, these studies do not explain herbivores such as horses and cows that have retained the Tas1r1 receptor.^[57]

Complete loss of T2R is known in some cartilaginous fishes and snakes.^[53][52]

Overall, the loss of function of the a taste receptor is an evolutionary process that occurred with a dietary change in species.^[58]