Pathway
Sensory perception of sweet, bitter, and umami (glutamate) taste
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.
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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, leukocytes, and enteroendocrine cells of the gut (inferred from rat and mouse homologs in Wu et al. 2002).
What the reference databases state
Statements
32 statements
32 statements · 1 reference database · Subject: Sensory perception of sweet, bitter, and umami (glutamate) taste · Sources: Reactome
- CALHM1 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- CALHM3 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- GNAT3 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- GNB1 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- GNB3 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- GNG13 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- GRM1 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- GRM4 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- ITPR3 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- PLCB2 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- SCN1B participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- SCN2A participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
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- SCN2B participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- SCN3A participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- SCN4B participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- SCN9A participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS1R1 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS1R2 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS1R3 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R1 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R10 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R13 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R14 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R20 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R3 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R38 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R39 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R40 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R5 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TAS2R8 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TRPM4 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only
- TRPM5 participates in Sensory perception of sweet, bitter, and umami (glutamate) tasteProteinReactome R-HSA-9717207Inferred only