Sensory perception of sweet, bitter, and umami (glutamate) taste

Stable Identifier
Homo sapiens
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Taste receptors for bitter compounds, sweet compounds, and umami compounds (L-glutamate in humans, several amino acids in mice) are G protein-coupled receptors located in type II taste bud cells that signal through a common downstream pathway (reviewed in Margolskee 2002, Kinnamon 2009, Kurihara 2015, Roper and Chauhari et al. 2017, Kinnamon and Finger 2019, Servant et al. 2020). Umami ("savoury", L-glutamate) taste receptors are heterodimers of the plasma membrane proteins TAS1R1 and TAS1R3. TAS1R1:TAS1R3 heterodimers also bind 5' nucleotides such as 5' IMP which synergistically augment umami taste. The glutamate receptors GRM1 (mGluR1) and GRM4 (mGluR4) act in an alternative pathway for sensing glutamate in taste cells (reviewed in Chaudhari et al. 2009). Sweet taste receptors are heterodimers of the plasma membrane proteins TAS1R2 and TAS1R3 (reviewed in Yang et al. 2021). The glucose transporters SGLT1 and GLUT4 are expressed in type II taste cells and may provide an alternative pathway for sensing glucose (reviewed in von Molitor et al. 2020). Bitter receptors are a large family of monomeric plasma membrane proteins, the TAS2R proteins.
TAS1R-containing sweet and umami receptors and TAS2R bitter receptors are each physically associated with a particular heterotrimeric G protein complex, the gustducin complex, containing GNAT3 (gustducin), GNB1 or GNB3, and GNG13. Upon binding an agonist ligand, the receptor activates the alpha subunit, GNAT3, to exchange GDP for GTP, which results in a conformational change in GNAT3 that causes the receptor-gustducin complex to dissociate, yielding GNAT3:GTP, GNB1,3:GNG13, and the receptor:ligand. The GNB1,3:GNG13 complex binds and activates Phospholipase C beta-2 (PLCB2), which then hydrolyzes phosphoinositol 4,5-bisphosphate (PI(4,5)P2) to yield diacylglycerol and inositol 1,4,5-trisphosphate (I(1,4,5)P3). I(1,4,5)P3 binds and activates the calcium channel IP3-gated Ca-channel type 3 (ITPR3) and ITPR3 then releases calcium ions from the endoplasmic reticulum into the cytosol. The increased cytosolic calcium activates the TRPM5 cation channels, which then transport sodium ions along the concentration gradient from the extracellular region to the cytosol (reviewed in Aroke et al. 2020). The depolarization activates SCN2A, SCN3A, and SCN9A channels, which transport further sodium ions from the extracellular region to the cytosol. The depolarization of the plasma membrane opens CALHM1:CALHM3 channels, which transport ATP, a neurotransmitter in the olfactory system, from the cytosol to the extracellular region.
Taste receptors were initially discovered in taste buds of the tongue and have now been found in several other tissues including nasal epithelium (Barnham et al. 2015, inferred from rodent homologs in Tizzano et al. 2011), the respiratory system, pancreatic islet cells, sperm (Governini et al. 2020), leukocytes (Malki et al. 2015), and enteroendocrine cells of the gut (inferred from rat and mouse homologs in Wu et al. 2002).

Literature References
PubMed ID Title Journal Year
31963712 Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm

Governini, L, Semplici, B, Pavone, V, Crifasi, L, Marrocco, C, De Leo, V, Arlt, E, Gudermann, T, Boekhoff, I, Luddi, A, Piomboni, P

J Clin Med 2020
32185015 Recent advances in taste transduction and signaling

Kinnamon, SC, Finger, TE

F1000Res 2019
32824721 Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

Aroke, EN, Powell-Roach, KL, Jaime-Lara, RB, Tesfaye, M, Roy, A, Jackson, P, Joseph, PV

Int J Mol Sci 2020
26247011 Umami the Fifth Basic Taste: History of Studies on Receptor Mechanisms and Role as a Food Flavor

Kurihara, K

Biomed Res Int 2015
23404938 Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa

Barham, HP, Cooper, SE, Anderson, CB, Tizzano, M, Kingdom, TT, Finger, TE, Kinnamon, SC, Ramakrishnan, VR

Int Forum Allergy Rhinol 2013
32607758 Current Progress in Understanding the Structure and Function of Sweet Taste Receptor

Yang, L, Cui, M, Liu, B

J Mol Neurosci 2021
11696554 Molecular mechanisms of bitter and sweet taste transduction

Margolskee, RF

J Biol Chem 2002
19571230 Taste receptors for umami: the case for multiple receptors

Chaudhari, N, Pereira, E, Roper, SD

Am J Clin Nutr 2009
19571214 Umami taste transduction mechanisms

Kinnamon, SC

Am J Clin Nutr 2009
33030576 An alternative pathway for sweet sensation: possible mechanisms and physiological relevance

von Molitor, E, Riedel, K, Krohn, M, Rudolf, R, Hafner, M, Cesetti, T

Pflugers Arch 2020
32416872 The function and allosteric control of the human sweet taste receptor

Servant, G, Kenakin, T, Zhang, L, Williams, M, Servant, N

Adv Pharmacol 2020
28655883 Taste buds: cells, signals and synapses

Roper, SD, Chaudhari, N

Nat Rev Neurosci 2017
25624459 Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes

Malki, A, Fiedler, J, Fricke, K, Ballweg, I, Pfaffl, MW, Krautwurst, D

J Leukoc Biol 2015
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