Tas1r3, encoding the T1R3 protein, is a crucial subunit of the heteromeric sweet taste (TAS1R2/TAS1R3) and umami taste (TAS1R1/TAS1R3) receptors. These receptors are part of the class-C G protein-coupling receptor (GPCR) family and play a vital role in detecting sweet and umami substances, which is important for food preference and energy intake regulation [2,4,5,6]. They are also involved in chemotaxis of human neutrophils and protection of T cells from activation-induced cell death in immune cells [1].

In mouse models, Tas1r3-deficient C57BL6/J mice have severely impaired responses to tuft cell-inducing signals in the distal small intestine, suggesting that Tas1r3 influences intestinal immunity by shaping the epithelial cell landscape at steady-state [3]. In F1 mouse hybrids, the recessive Tas1r3 allele is associated with reduced glucose tolerance, lower consumption of and lower preference for sweeteners [5]. Also, in a segregating congenic strain of mice, variation in the Tas1r3 gene affects the temporal properties of mouse brainstem taste responses to sweeteners, with the T1R2/T1R3 receptor initiating a separate, spatially distinct response after an initial T1R3-independent mechanism [6].

In summary, Tas1r3 is essential for taste perception, especially of sweet and umami substances, and also plays a role in glucose metabolism and intestinal immunity. The study of Tas1r3-deficient mouse models has provided valuable insights into its functions in these biological processes, which may have implications for understanding metabolic and immune-related diseases.

References:

1. Ball, Lena, Bauer, Julia, Krautwurst, Dietmar. 2023. Heterodimerization of Chemoreceptors TAS1R3 and mGlu2 in Human Blood Leukocytes. In International journal of molecular sciences, 24, . doi:10.3390/ijms241612942. https://pubmed.ncbi.nlm.nih.gov/37629122/

2. Behrens, Maik. . Pharmacology of TAS1R2/TAS1R3 Receptors and Sweet Taste. In Handbook of experimental pharmacology, 275, 155-175. doi:10.1007/164_2021_438. https://pubmed.ncbi.nlm.nih.gov/33582884/

3. Howitt, Michael R, Cao, Y Grace, Gologorsky, Matthew B, Regev, Aviv, Garrett, Wendy S. 2020. The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis. In ImmunoHorizons, 4, 23-32. doi:10.4049/immunohorizons.1900099. https://pubmed.ncbi.nlm.nih.gov/31980480/

4. Lin, Cailu, Tordoff, Michael G, Li, Xia, Bachmanov, Alexander A, Reed, Danielle R. 2021. Genetic controls of Tas1r3-independent sucrose consumption in mice. In Mammalian genome : official journal of the International Mammalian Genome Society, 32, 70-93. doi:10.1007/s00335-021-09860-w. https://pubmed.ncbi.nlm.nih.gov/33710367/

5. Murovets, Vladimir O, Lukina, Ekaterina A, Sozontov, Egor A, Khropycheva, Raisa P, Zolotarev, Vasiliy A. 2020. Allelic variation of the Tas1r3 taste receptor gene affects sweet taste responsiveness and metabolism of glucose in F1 mouse hybrids. In PloS one, 15, e0235913. doi:10.1371/journal.pone.0235913. https://pubmed.ncbi.nlm.nih.gov/32673349/

6. McCaughey, Stuart A. 2021. Variation in the gene Tas1r3 reveals complex temporal properties of mouse brainstem taste responses to sweeteners. In American journal of physiology. Regulatory, integrative and comparative physiology, 321, R751-R767. doi:10.1152/ajpregu.00001.2021. https://pubmed.ncbi.nlm.nih.gov/34523351/