Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity. G proteins are composed of 3 units; alpha, beta and gamma, respectively GNAT3, GNB1 and GNG13 for Gustducin heterotrimer for bitter taste transduction. The alpha chain contains the guanine nucleotide binding site. Gustducin heterotrimer may also be composed of GNAT3, GNB3 and GNG13. Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate and fungiform papillae of the tongue as well as in palatal taste buds at protein level. Expressed in enteroendocrine cells of the gut, such as in subsets of enteroendocrine cells in the midjejunum and brush cells. Detected also in spermatozoa. From week 1 to 7, the number of cells expressing GNAT3 in single taste buds increases within fungiform papilla; by week 7, the number reached the value found in adults. Expressed in cell bodies and axons of facial motor neurons at 10.5 dpc. Potential N-myristoylation may anchor alpha-subunit to the inner surface of plasma membrane. Mice are not affected in their tasting ability for salty (NaCl) and sour (HCl) stimuli, which are known not to be mediated by G proteins; but, they exhibit a significant reduction in the ability to taste the bitter compounds denatonium and quinine as well as the sweet compounds sucrose and SC45647, a guanidine sweetener. The incidence of cells responding to bitter stimulus is also reduced by seventy per cent. The residual behavioral response to bitter and sweet taste in these deficient mice suggests that there is alternative mechanism to compensate. However, transgenic expression of Gnat3 in these deficient mice restores responsiveness to both bitter and sweet compounds, whereas expression of mutated 'Gly-352' transgene do not. Furthermore, in wild-type mice, this mutated transgene acts as dominant-negative by inhibition of endogenous Gnat3 interactions with taste receptors. Mice show less preference for acesulfame-K, dulcin, fructose, D-phenylalanine, L-proline, D-tryptophan, saccharin, sweetener SC45647 and sucrose; Furthermore, in their gut, sugar or sweeteners do not increase SGLT1 expression and glucose-absorptive capacity compared to wild-type mice and the ingestion of glucose reveals deficiencies in secretion of GLP-1 and regulation of plasma insulin and glucose. Mice lacking GNAT3 show less preference for umami compounds such as monosodium glutamate (MSG) and no preference for inosine monophosphate (IMP) whereas wild-type mice strongly prefer IMP. The response to umami signals implicates the anteriorly placed taste buds of the tongue, and not the posterior part. Belongs to the G-alpha family. G(i/o/t/z) subfamily.