TAS2R38 Membrane Protein Introduction

Introduction of TAS2R38

Taste receptor type 2 member 38 (TAS2R38) belongs to G protein-coupled receptors family, which is encoded by TAS2R38 gene. Compared with other members of GPRs family, TAS2R38 also has an N-terminal extracellular domain, a C-terminal cytoplasmic domain, and a seven-transmembrane domain constituted with α-helix. Usually, the third α-helix is highly conservative revealing the important function of stability maintenance and receptor activation. TAS2R38 polymorphisms are very common in different populations, resulting in distinct sensitivity to bitter taste and food intake.

Function of TAS2R38 Membrane Protein

TAS2R38 is traditionally known as a member of taste receptor family 2 (T2R) bitter taste receptors, and it was originally identified in type 2 taste cells of the tongue, where it may play a role in the perception of bitterness or potentially harmful ingested chemicals and is gustducin-linked. The activation of TAS2R38 stimulates alpha G-protein gustducin, then mediates PLC-beta-2 activation and leads to the gating of TRPM5 (a calcium-activated non-selective cation channel), finally induces transmission of the taste signal. Recent research has demonstrated that TAS2R38 is also expressed in cilia of sinonasal epithelial cells, suggesting a role for TAS2R38 in sinonasal innate immunity and chronic rhinosinusitis. Activation of TAS2R38 in sinonasal epithelial cells can stimulate nitric oxide production, increasing ciliary beating and directly killing bacteria. Polymorphisms in TAS2R38 is closely linked to both impaired innate immune response and gram-negative infection and chronic rhinosinusitis (CRS). Furthermore, TAS2R38 may be associated with the risk of gastric cancer.

Fig.1 TAS2R38 in sinonasal innate immunity. (Lee, 2015)

Application of TAS2R38 Membrane Protein in Literature

1. Lee R.J and Cohen N.A. Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Current opinion in allergy and clinical immunology. 2015, 15(1): 14-20. PubMed ID: 25304231
   
   

   This article reports that beyond the type 2 taste cells of the tongue, T2R38 is also expressed in sinonasal-ciliated epithelial cells, where it detects bacterial quorum-sensing molecules and regulates nitric oxide-dependent innate immune responses. Genetic variation of TAS2R38 will decrease the innate immune response in the defense against bacteria.

2. Choi J.H., et al. Genetic variation in the TAS2R38 bitter taste receptor and gastric cancer risk in Koreans. Scientific reports. 2016, 6: 26904. PubMed ID: 27245112
   
   

   The authors demonstrate that gene variants of TAS2R38 are associated with alterations in individual sensitivity to bitter taste and food intake. And the variants may significantly increase the risk for diet-related diseases, such as gastric cancer.

3. Boxer E.E and Garneau N.L. Rare haplotypes of the gene TAS2R38 confer bitter taste sensitivity in humans. SpringerPlus. 2015, 4(1): 505. PubMed ID: 26405625
   
   

   This article presents 6-n-propylthiouracil (PROP) sensitivity data of 97 individuals that have been observed to carry rare haplotypes (AAV, AAI, PAI, PVI) of the TAS2R38 gene. They found the PAV haplotype is the most sensitive to taste, the AAI, AAV, and PAI haplotypes present intermediate taste sensitivity.

4. Dżaman K., et al. The correlation of TAS2R38 gene variants with higher risk for chronic rhinosinusitis in Polish patients. Otolaryngologia polska= The Polish otolaryngology. 2016, 70(5): 13-18. PubMed ID: 27935538
   
   

   This article reveals that TAS2R38 is highly expressed in sinus mucosa (SM) of chronic rhinosinusitis (CRS) patients. The genotypes PAV and AVI are very common in patients with CRS. The protective genotype (PAV/PAV) is noticed in the lowest frequency.

5. Pham H., et al. A bitter pill for type 2 diabetes? The activation of bitter taste receptor TAS2R38 can stimulate GLP-1 release from enteroendocrine L-cells. Biochemical and biophysical research communications. 2016, 475(3): 295-300. PubMed ID: 27208775
   
   

   This article indicates that TAS2R38 plays a major role in glucagon-like peptide 1 (GLP-1) release. And the gastrointestinal (GI) lumen location of TAS2R38 is a relatively safe drug target as systemic absorption is not needed for a TAS2R38 agonist drug to effect GLP-1 release.

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Reference

1. Lee R J and Cohen N A. (2015). Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Current opinion in allergy and clinical immunology. 15(1), 14-20.

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