TAS2R10 explained

Taste receptor type 2 member 10 is a protein that in humans is encoded by the TAS2R10 gene.^{[1] [2] [3]} The protein is responsible for bitter taste recognition in mammals. It serves as a defense mechanism to prevent consumption of toxic substances which often have a characteristic bitter taste.^[4]

Function

TAS2R10 is a G-protein-coupled receptor (GPCR) that is part of a large group of eukaryotic membrane receptors.^{[5] [6]} As a G-protein linked receptor, TAS2R10 helps with relaying communication across the cell membrane between the extracellular and intracellular matrix. Signaling molecules (ligands) bind to GPCRs and cause activation of the G protein which leads to activation of second messenger systems. These messengers inform cells of the presence or lack of substances in their environment which signals effectors to carryout biological functions.

TAS2R10 specifically acts as a bitter taste receptor.^[7] In general, TAS1Rs are receptors for umami and sweet tastes and TAS2Rs are bitter receptors. Bitter taste is mediated by numerous receptors, with TAS2R10 being part of a G-protein-coupled receptor superfamily. Humans have almost 1,000 different and highly specific GPCRs. Each GPCRs binds to a specific signaling molecule.

TAS2R10, along with several other bitter taste receptors, is expressed in the taste receptor cells of the tongue palate epithelia and smooth muscle of human airways. They are organized in the genome in clusters and are genetically linked to loci that influence bitter taste perception of both mice and humans. The activation of the receptors within cells causes an increase in intracellular calcium ions which triggers the opening of potassium channels. The cell membrane becomes depolarized and the smooth muscle relaxes. The depolarization stimulates neurotransmitters that send sensory information to the brain. The information is processed in the brain and perceived as a specific taste.

Structure

Most GPCRs consist of a single polypeptide with a globular tertiary shape and are made up of three general components: the extracellular domain, intracellular domain and the transmembrane domain.^[8] The extracellular domain includes the amino terminus and is composed of loops and helices that form binding pockets for ligands. Ligands bind to the receptors which causes activation.

The transmembrane domain consists of seven hydrophobic transmembrane segments. The segments are dispersed throughout the membrane. They transmit signals received from ligand binding at the extracellular domain to the intracellular domain.

The intracellular domain in the cytoplasm of the cell includes the carboxyl terminus and is where downstream signaling pathways are initiated as part of G-protein activation.

GPCR proteins range in size from 25-150 amino acids attached to the C- terminus and can be 80-480 Å in length.^[9]

Biological importance

In mammals, bitter taste is used as a safety mechanism to prevent animals from eating toxic plants or animals.^[10] Bitter taste serves as a warning that a substance is potentially lethal. TAS2R10 is one of many bitter taste receptors that allows for the recognition of bitter taste. TAS2R10 receptors are able to detect many toxic substances such as strychnine. Strychnine is a naturally occurring poisonous alkaloid found in the seeds of trees in the Strychnos genus. Ingestion or exposure of strychnine can cause involuntary muscle contractions and spasms that can lead to death by asphyxiation when respiratory muscles are involved.

Therapeutic use

A variety of research and studies are being conducted to investigate how taste receptors like TASR10 have additional functions beyond taste recognition. It is known that the activation of GPCR membrane proteins induces smooth muscle relaxation and vasodilation.^[11] This mechanism is being further studied in the hopes of developing potential treatments for vasoconstricting conditions such as asthma.^[12]

There is also research being down on how TASR receptors have a role in both regulatory functions in cancers and thyroid function regulation.^[13]

See also

• Taste receptor

Further reading

• Kinnamon SC . A plethora of taste receptors . Neuron . 25 . 3 . 507–510 . March 2000 . 10774719 . 10.1016/S0896-6273(00)81054-5 . free .
• Margolskee RF . Molecular mechanisms of bitter and sweet taste transduction . The Journal of Biological Chemistry . 277 . 1 . 1–4 . January 2002 . 11696554 . 10.1074/jbc.R100054200 . free .
• Montmayeur JP, Matsunami H . Receptors for bitter and sweet taste . Current Opinion in Neurobiology . 12 . 4 . 366–371 . August 2002 . 12139982 . 10.1016/S0959-4388(02)00345-8 . 37807140 .
• Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ . T2Rs function as bitter taste receptors . Cell . 100 . 6 . 703–711 . March 2000 . 10761935 . 10.1016/S0092-8674(00)80706-0 . 7293493 . free .
• Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ . Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways . Cell . 112 . 3 . 293–301 . February 2003 . 12581520 . 10.1016/S0092-8674(03)00071-0 . 718601 . free .
• Fischer A, Gilad Y, Man O, Pääbo S . Evolution of bitter taste receptors in humans and apes . Molecular Biology and Evolution . 22 . 3 . 432–436 . March 2005 . 15496549 . 10.1093/molbev/msi027 . free .
• Go Y, Satta Y, Takenaka O, Takahata N . Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates . Genetics . 170 . 1 . 313–326 . May 2005 . 15744053 . 1449719 . 10.1534/genetics.104.037523 .
• Mueller KL, Hoon MA, Erlenbach I, Chandrashekar J, Zuker CS, Ryba NJ . The receptors and coding logic for bitter taste . Nature . 434 . 7030 . 225–229 . March 2005 . 15759003 . 10.1038/nature03352 . 4383273 . 2005Natur.434..225M .

Notes and References

1. Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS . A novel family of mammalian taste receptors . Cell . 100 . 6 . 693–702 . March 2000 . 10761934 . 10.1016/S0092-8674(00)80705-9 . 14604586 . free .
2. Matsunami H, Montmayeur JP, Buck LB . A family of candidate taste receptors in human and mouse . Nature . 404 . 6778 . 601–604 . April 2000 . 10766242 . 10.1038/35007072 . 4336913 . 2000Natur.404..601M .
3. Web site: Entrez Gene . U.S. National Library of Medicine . TAS2R10 taste receptor, type 2, member 10.
4. Born S, Levit A, Niv MY, Meyerhof W, Behrens M . The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands . The Journal of Neuroscience . 33 . 1 . 201–213 . January 2013 . 23283334 . 6618634 . 10.1523/JNEUROSCI.3248-12.2013 .
5. GPCR Learn Science at Scitable . 2023-04-27 . Nature . en.
6. Book: Prinetti A, Mauri L, Chigorno V, Sonnino S . Lipid Membrane Domains in Glycobiology . 2007 . Comprehensive Glycoscience . 697–731 . 2023-04-27 . Elsevier . en . 10.1016/B978-044451967-2/00070-2 . 978-0-444-51967-2 .
7. TAS2R10 taste 2 receptor member 10 [Homo sapiens (human)] ]. National Center for Biotechnology Information (NCBI) . U.S. National Library of Medicine . 2023-04-27 .
8. Kobilka BK . G protein coupled receptor structure and activation . Biochimica et Biophysica Acta . 1768 . 4 . 794–807 . April 2007 . 17188232 . 1876727 . 10.1016/j.bbamem.2006.10.021 .
9. Gurevich VV, Gurevich EV . GPCR monomers and oligomers: it takes all kinds . Trends in Neurosciences . 31 . 2 . 74–81 . February 2008 . 18199492 . 2366802 . 10.1016/j.tins.2007.11.007 .
10. Reed DR, Knaapila A . Genetics of taste and smell: poisons and pleasures . Progress in Molecular Biology and Translational Science . 94 . 213–240 . 2010 . 21036327 . 3342754 . 10.1016/B978-0-12-375003-7.00008-X .
11. Zhu H, Liu L, Ren L, Ma J, Hu S, Zhu Z, Zhao X, Shi C, Wang X, Zhang C, Gu M, Li X . Systematic prediction of the biological functions of TAS2R10 using positive co-expression analysis . Experimental and Therapeutic Medicine . 19 . 3 . 1733–1738 . March 2020 . 32104227 . 7027137 . 10.3892/etm.2019.8397 .
12. Doggrell SA . Bitter taste receptors as a target for bronchodilation . Expert Opinion on Therapeutic Targets . 15 . 7 . 899–902 . July 2011 . 21521131 . 10.1517/14728222.2011.580279 . 34827994 .
13. Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, Steinle NI, Munger SD . TAS2R bitter taste receptors regulate thyroid function . FASEB Journal . 29 . 1 . 164–172 . January 2015 . 25342133 . 4285546 . 10.1096/fj.14-262246 . free .