TAS2R46 Membrane Protein Introduction

Introduction of TAS2R46

TAS2R46 is also known as taste receptor type 2 member 46 (T2R46), which in humans is encoded by the TAS2R46 gene, that is mapped to chromosome 12p13.2. TAS2R46 is a member of the large TAS2R receptor family. Acted as a candidate taste receptor, TAS2R46 is specifically expressed in the taste receptor cells of our tongue and palate epithelia. Belonging to GPCR superfamily, TAS2R46 is organized in the genome in clusters and is genetically linked to loci that influence bitter perception.

Function ofTAS2R46 Membrane Protein

TAS2Rs, a family of G protein-coupled receptors (GPCRs), are responsible for the perception of bitter taste, which is important for the evaluation of food quality and the nutritional control in human and animals. TAS2Rs are expressed in specialized sensory cells (predominant bitter taste cells on our tongue) and mediate bitterness signals through the activation of correspondent G proteins. Research showed that human bone marrow stromal-derived cells (MSC) can also express TAS2R46 receptor, besides the more typical localization of the taste bud. As a bitter receptor, TAS2R46 has been proved to broadly sense a large variety of putative bitter tastants, such as sesquiterpene lactones, labdane diterpenes, related clerodane diterpenoids and more. Moreover, TAS2R46 is reported to play a role in sensing the chemical composition of the gastrointestinal content. It is reported that the activated TAS2R46 receptor may cause α-gustducin stimulated, mediate PLC-beta-2 activation, and result in the gating of TRPM5. In airway epithelial cells, binding of bitter compounds can raise the intracellular Ca²⁺ concentration and increase ciliary beat frequency. From the predicted results performed using TOPCONS, TAS2R46 possesses 7 transmembrane regions and 2 glycosylation sites (161 and 176), which are important for its function in sensory cells.

Fig.1 Taste receptors of the tongue are present in the taste buds of papillae. (Ayana, 2012)

Application of TAS2R46 Membrane Protein in Literature

1. Sandal M., et al. Evidence for a transient additional ligand binding site in the tAS2R46 bitter taste receptor. J Chem Theory Comput. 2015, 11(9): 4439-49. PubMed ID: 26575934
   
   

   This article reveals that a typical agonist of TAS2R46, a prototypical broad-spectrum chemosensory GPCR, features two cavities recognition process. Moreover, it also suggests, on the basis of bioinformatics analysis, that both cavities could be involved in receptor selectivity. This seems to be apt to chemosensory function. A single binding site may not contain enough information, encoded as potential side chain/ligand contacts, to discriminate between chemically similar compounds while also accept a wide spectrum of chemically different compounds, as it happens in bitter taste receptors.

2. Yamaki M., et al. Genotyping analysis of bitter-taste receptor genes TAS2R38 and TAS2R46 in Japanese patients with gastrointestinal cancers. J Nutr Sci Vitaminol (Tokyo). 2017, 63(2): 148-154. PubMed ID: 28552880
   
   

   This article conducts a explorative study by genotyping TAS2R46, in many Japanese cancer patients diagnosed with the following types of cancer: biliary tract cancer, pancreatic cancer, hepatocellular carcinoma, gastric cancer and colorectal cancer, and then finds that cancer risk has no connection with any genotypes of TAS2R46 since there are no notable differences in genotype frequencies between cancer patients and controls.

3. Barham HP., et al. Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa. PLoS One. 2013, 3(6): 450-7. PubMed ID: 23404938
   
   

   This article demonstrates that bitter taste receptors TAS2R14, TAS2R46, and TAS2R4, and downstream signaling effectors PLCβ2, α-Gustducin, and TRPM5 are expressed in the inferior turbinate, septum, middle turbinate, and uncinate of both diseased patients and control by RT-PCR.

4. Suess B., et al. The odorant (R)-citronellal attenuates caffeine bitterness by inhibiting the bitter receptors TAS2R43 and TAS2R46. J Agric Food Chem. 2018, 66(10): 2301-2311. PubMed ID: 27569025
   
   

   This article reveals (R)-citronellal completely block caffeine-induced calcium signals in TAS2R43-expressing cells, and, to a lesser extent, in TAS2R46-expressing cells.

5. Born S., et al. The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands. J Neurosci. 2013, 33(1): 201-13. PubMed ID: 23283334
   
   

   This article reveals that engineering the key determinants for TAS2R46 activation by strychnine in TAS2R10 may lead to a loss of response to strychnine, and some paralog receptors display different strychnine-binding modes. It also implies that the gene duplication event preceding primate speciation is accompanied by independent evolution of the strychnine-binding sites.

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Reference

1. Ayana Wiener, et al. (2012). A database of bitter compounds. Nucleic Acids Res. 40(Database issue), D413-419.

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