TAS1R1

{{short description|Protein}}

{{Infobox_gene}}

Taste receptor type 1 member 1 is a protein that in humans is encoded by the TAS1R1 gene.{{cite web | title = Entrez Gene: TAS1R1 taste receptor, type 1, member 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80835}}

Structure

The protein encoded by the TAS1R1 gene is a G protein-coupled receptor with seven trans-membrane domains and is a component of the heterodimeric amino acid taste receptor T1R1+3. This receptor is formed as a dimer of the TAS1R1 and TAS1R3 proteins. Moreover, the TAS1R1 protein is not functional outside of formation of the 1+3 heterodimer.{{cite journal | vauthors = Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS | title = Mammalian sweet taste receptors | journal = Cell | volume = 106 | issue = 3 | pages = 381–390 | year = 2001 | pmid = 11509186 | doi = 10.1016/S0092-8674(01)00451-2 | s2cid = 11886074 | doi-access = free }} The TAS1R1+3 receptor has been shown to respond to L-amino acids but not to their D-enantiomers or other compounds. This ability to bind L-amino acids, specifically L-glutamine, enables the body to sense the umami, or savory, taste.{{cite journal | vauthors = Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS | title = An amino-acid taste receptor | journal = Nature | volume = 416 | issue = 6877 | pages = 199–202 | year = 2002 | pmid = 11894099 | doi = 10.1038/nature726 | bibcode = 2002Natur.416..199N | s2cid = 1730089 }} Multiple transcript variants encoding several different isoforms have been found for this gene, which may account for differing taste thresholds among individuals for the umami taste.{{cite journal | vauthors = White BD, Corll CB, Porter JR | title = The metabolic clearance rate of corticosterone in lean and obese male Zucker rats | journal = Metabolism: Clinical and Experimental | volume = 38 | issue = 6 | pages = 530–536 | year = 1989 | pmid = 2725291 | doi=10.1016/0026-0495(89)90212-6}} Another interesting quality of the TAS1R1 and TAS1R2 proteins is their spontaneous activity in the absence of the extracellular domains and binding ligands.{{cite journal | vauthors = Sainz E, Cavenagh MM, LopezJimenez ND, Gutierrez JC, Battey JF, Northup JK, Sullivan SL | title = The G-protein coupling properties of the human sweet and amino acid taste receptors | journal = Developmental Neurobiology | volume = 67 | issue = 7 | pages = 948–959 | year = 2007 | pmid = 17506496 | doi = 10.1002/dneu.20403 | s2cid = 29736077 }} This may mean that the extracellular domain regulates function of the receptor by preventing spontaneous action as well as binding to activating ligands such as L-glutamine.

Ligands

The umami taste is distinctly related to the compound monosodium glutamate (MSG). Synthesized in 1908 by Japanese chemist Kikunae Ikeda, this flavor-enhancing compound led to the naming of a new flavor quality that was named “umami”, the Japanese word for “tasty”.{{cite journal |last=Sand |first=Jordan |year=2005 |title= A Short History of MSG: Good Science, Bad Science, and Taste Cultures |journal= Gastronomica: The Journal of Food and Culture|volume=5 |issue=4 |pages=38–49 |publisher=University of California Press |doi= 10.1525/gfc.2005.5.4.38}} The TAS1R1+3 taste receptor is sensitive to the glutamate in MSG as well as the synergistic taste-enhancer molecules inosine monophosphate (IMP) and guanosine monophosphate (GMP). These taste-enhancer molecules are unable to activate the receptor alone, but are rather used to enhance receptor responses to many L-amino acids.{{cite journal | vauthors = Delay ER, Beaver AJ, Wagner KA, Stapleton JR, Harbaugh JO, Catron KD, Roper SD | title = Taste preference synergy between glutamate receptor agonists and inosine monophosphate in rats | journal = Chemical Senses | volume = 25 | issue = 5 | pages = 507–515 | year = 2000 | pmid = 11015322 | doi = 10.1093/chemse/25.5.507 | doi-access = free }}

Signal transduction

TAS1R1 and TAS1R2 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gustducin knock-out has shown small residual activity. TAS1R1 and TAS1R2 have also been shown to activate Gαo and Gαi. This suggests that TAS1R1 and TAS1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.{{cite journal | vauthors = Abaffy T, Trubey KR, Chaudhari N | title = Adenylyl cyclase expression and modulation of cAMP in rat taste cells | journal = American Journal of Physiology. Cell Physiology | volume = 284 | issue = 6 | pages = C1420–C1428 | year = 2003 | pmid = 12606315 | doi = 10.1152/ajpcell.00556.2002 | s2cid = 2704640 }}

Research done by creating knock-outs of common channels activated by sensory G-protein second messenger systems has also shown a connection between umami taste perception and the phosphatidylinositol (PIP2) pathway. The nonselective cation Transient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, the phospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.{{cite journal | vauthors = Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ | title = Coding of sweet, bitter, and umami tastes: Different receptor cells sharing similar signaling pathways | journal = Cell | volume = 112 | issue = 3 | pages = 293–301 | year = 2003 | pmid = 12581520 | doi = 10.1016/S0092-8674(03)00071-0 | s2cid = 718601 | doi-access = free }}

Location and innervation

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. 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.{{cite journal | vauthors = Danilova V, Hellekant G | title = Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice | journal = BMC Neuroscience | volume = 4 | pages = 5–6 | year = 2003 | pmid = 12617752 | pmc = 153500 | doi = 10.1186/1471-2202-4-5 | doi-access = free }} TAS1R and TAS2R (bitter) channels are not expressed together in taste buds.

See also

References

{{reflist|35em}}

Further reading

{{refbegin|35em}}

  • {{cite journal | vauthors = Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS | title = The receptors and cells for mammalian taste. | journal = Nature | volume = 444 | issue = 7117 | pages = 288–94 | year = 2007 | pmid = 17108952 | doi = 10.1038/nature05401 | bibcode = 2006Natur.444..288C | s2cid = 4431221 }}
  • {{cite journal | vauthors = Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS | title = Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. | journal = Cell | volume = 96 | issue = 4 | pages = 541–51 | year = 1999 | pmid = 10052456 | doi = 10.1016/S0092-8674(00)80658-3 | s2cid = 14773710 | doi-access = free }}
  • {{cite journal | vauthors = Makalowska I, Sood R, Faruque MU, Hu P, Robbins CM, Eddings EM, Mestre JD, Baxevanis AD, Carpten JD | title = Identification of six novel genes by experimental validation of GeneMachine predicted genes. | journal = Gene | volume = 284 | issue = 1–2 | pages = 203–13 | year = 2002 | pmid = 11891061 | doi = 10.1016/S0378-1119(01)00897-6 }}
  • {{cite journal | vauthors = Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS | title = An amino-acid taste receptor. | journal = Nature | volume = 416 | issue = 6877 | pages = 199–202 | year = 2002 | pmid = 11894099 | doi = 10.1038/nature726 | bibcode = 2002Natur.416..199N | s2cid = 1730089 }}
  • {{cite journal | vauthors = Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E | title = Human receptors for sweet and umami taste. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 7 | pages = 4692–6 | year = 2002 | pmid = 11917125 | pmc = 123709 | doi = 10.1073/pnas.072090199 | bibcode = 2002PNAS...99.4692L | doi-access = free }}
  • {{cite journal | vauthors = Liao J, Schultz PG | title = Three sweet receptor genes are clustered in human chromosome 1. | journal = Mamm. Genome | volume = 14 | issue = 5 | pages = 291–301 | year = 2003 | pmid = 12856281 | doi = 10.1007/s00335-002-2233-0 | s2cid = 30665284 }}
  • {{cite journal | vauthors = Xu H, Staszewski L, Tang H, Adler E, Zoller M, Li X | title = Different functional roles of T1R subunits in the heteromeric taste receptors. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 39 | pages = 14258–63 | year = 2005 | pmid = 15353592 | pmc = 521102 | doi = 10.1073/pnas.0404384101 | bibcode = 2004PNAS..10114258X | doi-access = free }}
  • {{cite journal | vauthors = Sainz E, Cavenagh MM, LopezJimenez ND, Gutierrez JC, Battey JF, Northup JK, Sullivan SL | title = The G-protein coupling properties of the human sweet and amino acid taste receptors. | journal = Dev Neurobiol | volume = 67 | issue = 7 | pages = 948–59 | year = 2007 | pmid = 17506496 | doi = 10.1002/dneu.20403 | s2cid = 29736077 }}

{{refend}}