Affinage

GNAT3

Guanine nucleotide-binding protein G(t) subunit alpha-3 · UniProt A8MTJ3

Length
354 aa
Mass
40.4 kDa
Annotated
2026-06-10
87 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GNAT3 (alpha-gustducin) is a taste cell-specific Gα subunit that transduces bitter, sweet, and umami chemosensation and, more broadly, serves as a chemosensory G protein in non-gustatory epithelia (PMID:1608467, PMID:8657284, PMID:15342734). Cloned as a transducin-related Gα selectively expressed in taste buds, it is dually lipid-modified, exhibits receptor-catalyzed GDP-GTP exchange and intrinsic GTPase activity biochemically indistinguishable from transducin, and couples to upstream receptors and downstream phosphodiesterase effectors (PMID:1608467, PMID:7626029). In taste receptor cells it assembles into a heterotrimer with Gβ1/Gβ3 and Gγ13, concentrated in the apical microvilli of type II cells, where bitter stimuli trigger a bifurcated cascade: activated alpha-gustducin drives rapid reduction of cAMP/cGMP while liberated Gβγ activates PLCβ2 to generate IP3 within the same cell (PMID:10570481, PMID:10940948, PMID:11245589). Knockout, transgenic dominant-negative (G352P), and wild-type rescue genetics establish that the C-terminal receptor-interaction domain is causative for bitter and sweet responses, with a parallel Gαi2-dependent gustducin-independent pathway also contributing to bitter sensing (PMID:8657284, PMID:11447270, PMID:14586025). Beyond the tongue, alpha-gustducin acts in gut enteroendocrine and gastric cells to couple sweet (T1R2/T1R3), fatty-acid, and bile-acid receptors to GLP-1 and ghrelin secretion and to SGLT1 regulation, linking luminal nutrient sensing to glucose homeostasis and food intake (PMID:17724330, PMID:17724332, PMID:21245306, PMID:23341498). It tonically suppresses basal cAMP in both taste cells and pancreatic β-cells, restraining basal Ca2+ and insulin secretion (PMID:18930056, PMID:31957256). In epithelial and immune contexts it mediates anti-inflammatory bitter T2R signaling—inhibiting LPS-induced chemokine expression and NF-κB activation in gingival fibroblasts and airway cells—and restrains CXCL1/CXCL2-driven MDSC expansion to suppress pancreatic cancer progression (PMID:32882403, PMID:38605968, PMID:41596643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1992 High

    Established the molecular identity of a candidate taste transduction G protein, defining the gene whose function the field would dissect.

    Evidence cDNA cloning and Northern blot from taste tissue showing taste-bud-selective expression of a transducin-related Gα

    PMID:1608467

    Open questions at the time
    • Expression alone did not demonstrate functional coupling
    • No effector or receptor partner identified at this stage
  2. 1995 High

    Demonstrated that alpha-gustducin is a bona fide functional Gα with transducin-like enzymatic behavior, establishing that taste cells likely contain analogous receptors and PDE effectors.

    Evidence Baculovirus recombinant expression with in vitro reconstitution against rhodopsin, retinal cGMP-PDE, and Gβγ, plus GTPase/exchange assays

    PMID:7626029

    Open questions at the time
    • Used visual-system surrogates rather than authentic taste receptors/effectors
    • Did not identify the endogenous taste receptor or PDE
  3. 1996 High

    Provided the first in vivo proof that the gene mediates taste, unexpectedly implicating it in sweet as well as bitter transduction.

    Evidence Alpha-gustducin null mice with behavioral preference tests and chorda tympani nerve recordings

    PMID:8657284

    Open questions at the time
    • Residual responses indicated gustducin-independent pathways
    • Did not resolve the downstream second-messenger logic
  4. 1998 High

    Mapped where bitter ligands act on the transduction machinery, showing direct receptor-driven activation that requires the Gα C-terminus and Gβγ.

    Evidence In vitro activation assays with bitter compounds and taste membranes, peptide competition, and detergent solubilization of the bitter receptor

    PMID:9671782

    Open questions at the time
    • Bitter receptor not molecularly cloned here
    • Reconstitution used tissue membranes rather than purified receptor
  5. 1999 High

    Defined the heterotrimer composition and the bifurcated effector logic—Gα to PDE and Gβγ to PLCβ2/IP3—of bitter transduction.

    Evidence Co-immunolocalization, single-cell RT-PCR, heterotrimer activation assays, and Gγ13 antibody blocking of IP3 in taste tissue

    PMID:10570481

    Open questions at the time
    • Did not directly resolve cyclic-nucleotide kinetics
    • Relative contribution of Gβ1 vs Gβ3 left open
  6. 1999 High

    Identified a pharmacological modulator acting at the bitter receptor/G-protein interface, confirming specificity of the gustducin-coupled bitter pathway.

    Evidence In vitro GTP-binding assays plus behavioral and electrophysiological recordings showing AMP-class (but not GMP) inhibition of bitter responses

    PMID:10449792

    Open questions at the time
    • Exact molecular site of AMP action not pinpointed
    • Mechanism distinct from receptor antagonism not excluded
  7. 2000 Medium

    Localized the protein to the apical sensory surface, anchoring its biochemical role to the initial transduction event.

    Evidence Quantitative immunogold electron microscopy in type II taste cell microvilli

    PMID:10940948

    Open questions at the time
    • Single-species circumvallate analysis
    • Subcellular enrichment is correlative for function
  8. 2001 High

    Directly measured the predicted dual second-messenger response and assigned each arm to a distinct component, confirming pathway bifurcation in a single cell.

    Evidence Quench-flow radioimmunoassay of cAMP/cGMP/IP3 with isoform-specific PLCβ and alpha-gustducin antibody inhibition

    PMID:11245589

    Open questions at the time
    • Which PDE isoform alpha-gustducin regulates not identified
    • Coupling to downstream channel/Ca2+ release steps not fully traced
  9. 2001 High

    Formally proved causation by active-site mutagenesis, dominant-negative interference, and rescue, localizing function to the C-terminal receptor-interaction domain.

    Evidence G352P site-directed mutagenesis, transgenic dominant-negative and wild-type rescue mice, behavioral and nerve recordings

    PMID:11447270

    Open questions at the time
    • Did not address non-taste functions
    • Other domain functions not individually dissected
  10. 2002 Medium

    Tested functional substitutability against rod transducin, revealing that in-vitro-identical Gα proteins diverge in vivo for specific tastants.

    Evidence Transgenic rescue of null mice with rod alpha-transducin under the gustducin promoter, preference tests and nerve recordings

    PMID:12379596

    Open questions at the time
    • Molecular basis of the in vivo distinction unresolved
    • Only partial rescue of select compounds
  11. 2003 High

    Linked molecular identity to single-cell function and surfaced a parallel Gαi2-based bitter pathway, quantifying the gustducin-dependent fraction.

    Evidence Ca2+ imaging in lingual slices with post-hoc immunofluorescence comparing wild-type and knockout mice

    PMID:14586025

    Open questions at the time
    • Gαi2 role inferred from coexpression, not perturbed
    • Did not test sweet/umami cell populations
  12. 2004 High

    Extended the gene's sensory remit to umami and dissected G-protein redundancy across tongue regions by genetic epistasis.

    Evidence Behavior and nerve recordings in single and double alpha-gustducin/alpha-transducin knockout mice across umami tastants

    PMID:15342734

    Open questions at the time
    • Posterior umami G protein remains unidentified
    • Receptor coupling for IMP vs glutamate not resolved
  13. 2008 Medium

    Revealed a tonic, ligand-independent role in keeping basal cAMP low, explaining how loss elevates cAMP and dampens taste signaling.

    Evidence cAMP measurement in wild-type vs knockout taste buds with PKA inhibition (H-89) unmasking responses

    PMID:18930056

    Open questions at the time
    • Effector PDE/AC controlling tonic cAMP not identified
    • Single-lab pharmacological rescue
  14. 2007 High

    Established alpha-gustducin as a gut chemosensor coupling sweet/sugar sensing to incretin and transporter responses with metabolic consequences.

    Evidence KO mouse glucose/GLP-1 studies, ex vivo villi secretion, siRNA in NCI-H716, plus T1R3/gustducin KO SGLT1 mRNA/protein and absorption assays (two studies)

    PMID:17724330 PMID:17724332

    Open questions at the time
    • Downstream second-messenger steps in L cells not fully mapped
    • Relationship to the taste-cell dual cascade in enteroendocrine cells unresolved
  15. 2011 High

    Showed gastric bitter T2R sensing through alpha-gustducin regulates ghrelin secretion, food intake, and hypothalamic appetite signaling.

    Evidence T2R agonist gavage in alpha-gustducin KO mice with plasma ghrelin RIA, food intake, and AgRP mRNA

    PMID:21245306

    Open questions at the time
    • Effect was only partially blunted in KO
    • Direct receptor-Gα coupling in ghrelin cells not biochemically shown
  16. 2013 High

    Broadened gut chemosensing to fatty-acid and bile-acid receptors, positioning alpha-gustducin as a hub coupling diverse nutrient GPCRs to GLP-1 release.

    Evidence Colocalization and ex vivo colonic mucosa GLP-1 secretion assays in KO vs wild-type across multiple agonists

    PMID:23341498

    Open questions at the time
    • Direct physical coupling to each GPCR not demonstrated
    • Cellular signaling intermediates not resolved
  17. 2018 Medium

    Implicated alpha-gustducin in gut mucosal immune homeostasis, extending its role beyond secretion to inflammation control.

    Evidence DSS-induced colitis in alpha-gustducin KO mice with histology, immune infiltration, and cytokine mRNA profiling

    PMID:29678794

    Open questions at the time
    • Cell type and receptor mediating the protective effect unclear
    • Single-lab phenotype
  18. 2020 High

    Defined a tumor-suppressive function in pancreatic tuft cells via restraint of CXCL1/CXCL2 and MDSC expansion.

    Evidence Gnat3-null KRAS mouse models, organoid cytokine profiling, mass cytometry, scRNA-seq, and tumor progression analysis

    PMID:32882403

    Open questions at the time
    • Upstream receptor and signaling linking Gnat3 to chemokine suppression not defined
    • Whether the dual cAMP/PLC cascade operates here unknown
  19. 2020 Medium

    Demonstrated a taste-receptor-independent tonic suppression of basal cAMP, Ca2+, and insulin in β-cells, paralleling its taste-cell role.

    Evidence siRNA knockdown of alpha-gustducin in INS-1 β-cells with cAMP, Ca2+, and insulin assays

    PMID:31957256

    Open questions at the time
    • Single cell line; not confirmed in primary islets in vivo
    • Effector controlling tonic cAMP not identified
  20. 2024 High

    Showed alpha-gustducin is required for anti-inflammatory bitter T2R signaling in gingival fibroblasts, linking chemosensation to chemokine and bone-loss control.

    Evidence Heterologous Tas2r143/Gα-gustducin expression with calcium imaging, receptor siRNA, and Gnat3-/- ligature periodontitis model

    PMID:38605968

    Open questions at the time
    • Mechanistic link from Ca2+ signal to chemokine suppression not resolved
    • Generality across other gingival T2Rs untested
  21. 2026 Medium

    Established that GNAT3 is required for bitter-agonist suppression of NF-κB-driven inflammation in airway epithelium.

    Evidence siRNA knockdown of GNAT3 in BEAS-2B cells with NF-κB phospho-readouts (p-p65, p-IκB) across multiple bitter agonists

    PMID:41596643

    Open questions at the time
    • Signaling steps between GNAT3 and NF-κB not mapped
    • Single cell line knockdown only

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the endogenous phosphodiesterase/effector that alpha-gustducin regulates to set tonic cAMP, and how the canonical taste dual cascade relates to its non-gustatory immune and tumor-suppressive functions, remain unresolved.
  • No PDE effector molecularly identified across tissues
  • Mechanism connecting Gα activation to chemokine/NF-κB suppression undefined
  • Receptor-Gα coupling in extragustatory cells not biochemically reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0003924 GTPase activity 2
Localization
GO:0005856 cytoskeleton 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-9709957 Sensory Perception 3
Partners
GNB1GNB3GNG13PLCB2TAS1R3
Complex memberships
Gustducin heterotrimer (Gα-gustducin/Gβ1/Gγ13)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Alpha-gustducin (GNAT3) was identified and cloned from taste tissue as a novel G protein alpha-subunit selectively expressed in taste buds of all taste papillae; it is most closely related to the transducins (rod and cone photoreceptor G proteins), suggesting a transducin-analogous role in taste transduction. cDNA cloning, Northern blot (tissue expression), sequence analysis Nature High 1608467
1995 Recombinant alpha-gustducin expressed in baculovirus is myristoylated and palmitoylated. It interacts functionally with rhodopsin (receptor), bovine retinal cGMP-phosphodiesterase (effector), and G-protein beta-gamma heterodimers; its receptor-catalyzed GDP-GTP exchange and intrinsic GTPase activity are quantitatively identical to those of alpha-transducin, suggesting taste cells contain analogous receptor and effector proteins. Baculovirus recombinant protein expression, purification, in vitro reconstitution with visual system components, GTPase and GDP-GTP exchange assays The Biochemical journal High 7626029
1993 Rod and cone transducins were also cloned from taste cells (first identification outside photoreceptors). The primary sequence of alpha-gustducin shares similarities with transducins at the receptor interaction domain and phosphodiesterase activation site, suggesting gustducin and transducin regulate taste cell phosphodiesterase in bitter taste transduction. PCR cloning of G-protein alpha-subunit cDNAs from rat taste cell library, sequence analysis Ciba Foundation symposium Medium 8168377
1996 Alpha-gustducin is a principal mediator of both bitter and sweet signal transduction in vivo. Alpha-gustducin knockout mice showed markedly reduced behavioral and electrophysiological responses to bitter compounds and, unexpectedly, also to sweet compounds, while responses to salty and sour stimuli were normal. Genetic knockout (alpha-gustducin null mice), behavioral taste preference tests, electrophysiological chorda tympani nerve recordings Nature High 8657284
1998 Gustducin and transducin are activated in vitro by bitter compounds (denatonium, quinine, strychnine) in the presence of bovine taste membranes. Activation requires the C-terminal region of gustducin and G-protein beta-gamma subunits. Peptides derived from the rhodopsin-transducin interaction sites competitively inhibit taste receptor-gustducin coupling. The bitter-responsive receptor was solubilized while retaining biological activity. In vitro GTPase/GTP-binding activation assay with taste membranes and bitter compounds, peptide competition assay, detergent solubilization Proceedings of the National Academy of Sciences of the United States of America High 9671782
1999 Ggamma13 colocalizes with alpha-gustducin in taste receptor cells; ~80% of alpha-gustducin/Ggamma13 cells also express Gbeta3 and ~80% express Gbeta1. Gustducin heterotrimers (alpha-gustducin/Gbeta1/Ggamma13) are activated by taste cell membranes plus bitter denatonium. Antibodies against Ggamma13 block denatonium-induced IP3 increase in taste tissue. The bitter transduction mechanism involves alpha-gustducin regulating phosphodiesterase (cAMP/cGMP) and Gbetagamma activating phospholipase C beta2 (IP3 pathway). Co-immunolocalization, single-cell RT-PCR profiling, in vitro heterotrimer activation assay, antibody blocking of IP3 production in taste tissue Nature neuroscience High 10570481
1999 AMP and chemically related nucleotides inhibit the bitter-responsive taste receptor activation of transducin/gustducin in vitro and inhibit behavioral and electrophysiological responses to bitter tastants (denatonium, quinine, strychnine, atropine) in mice, but not responses to NaCl, HCl, or sucrose. GMP does not inhibit, indicating specificity. AMP compounds act at bitter-responsive taste receptors or receptor-G protein interface. In vitro GTP-binding activation assay, behavioral preference tests, electrophysiological nerve recordings in mice Proceedings of the National Academy of Sciences of the United States of America High 10449792
2000 Alpha-gustducin immunoreactivity is concentrated in microvilli of type II taste cells (not type I cells) in rat circumvallate papillae, with approximately 2.5 times more colloidal gold particles in microvilli versus cytoplasm, consistent with a role in initial sensory transduction events at the apical membrane. Immunoelectron microscopy with quantitative immunogold labeling The Journal of comparative neurology Medium 10940948
2001 Bitter stimuli (denatonium, strychnine) induce rapid (50-100 ms) and transient reductions in both cAMP and cGMP, and increases in IP3 in murine taste tissue. The cyclic nucleotide decrease is inhibited by alpha-gustducin antibodies; the IP3 increase is not affected by alpha-gustducin antibodies but is inhibited by antibodies to PLCbeta2 (not PLCbeta3 or PLCbeta4). This establishes that alpha-gustducin mediates cyclic nucleotide decreases while Gbetagamma (likely Gbeta1/Ggamma13) activates PLCbeta2 for IP3 production, both in the same bitter-stimulated cell. Quench-flow technique with radioimmunoassay for cAMP, cGMP, and IP3; antibody inhibition with isoform-specific PLCbeta antibodies in taste tissue American journal of physiology. Cell physiology High 11245589
2001 A single point mutation G352P in the C-terminal region of alpha-gustducin critical for receptor interaction renders the protein unable to be activated by taste receptors while leaving other functions intact. Transgenic expression of this dominant-negative alpha-gustducin in wild-type mice inhibited endogenous gustducin's taste receptor interactions and further reduced bitter and sweet taste responsiveness. Transgenic rescue with wild-type alpha-gustducin in null mice fully restored bitter and sweet responses, formally proving the gene's causative role. Site-directed mutagenesis (G352P), transgenic mouse generation, dominant-negative analysis, behavioral taste tests, nerve recordings Proceedings of the National Academy of Sciences of the United States of America High 11447270
2002 Transgenic expression of rod alpha-transducin under the alpha-gustducin promoter in alpha-gustducin null mice partially rescued behavioral and electrophysiological responses to some sweet and bitter compounds (sucrose, SC45647, quinine) but not others (denatonium). Alpha-gustducin and alpha-transducin, although biochemically indistinguishable in vitro, differ at least partly in their in vivo taste cell function. Transgenic rescue (alpha-transducin under gustducin promoter in null background), two-bottle preference tests, chorda tympani nerve recordings Chemical senses Medium 12379596
2003 Direct cellular correlation: Ca2+ imaging in lingual slices showed that the incidence of taste cells responding to bitter stimuli was reduced by 70% in alpha-gustducin knockout mice versus wild-type. Bitter-responding cells in wild-type mostly, but not all, expressed alpha-gustducin. Galpha-i2 was found in most bitter-responsive cells including those lacking alpha-gustducin, suggesting Galpha-i2 may contribute to the gustducin-independent bitter response pathway. Ca2+ imaging in lingual slices combined with post-hoc immunofluorescence for alpha-gustducin; comparison between wild-type and knockout mice The Journal of neuroscience High 14586025
2004 Alpha-gustducin mediates umami taste (monosodium glutamate, monopotassium glutamate, inosine monophosphate). Double knockout of alpha-gustducin and rod alpha-transducin showed that alpha-transducin contributes to MSG and MPG umami taste (not IMP) in anteriorly placed taste buds, while posterior taste cells respond to umami independently of both G proteins. Behavioral tests and chorda tympani nerve recordings in single and double knockout mice (alpha-gustducin KO, alpha-transducin KO, and double KO) The Journal of neuroscience High 15342734
2007 Intestinal L cells express alpha-gustducin, sweet taste receptors (T1R2/T1R3), and other taste transduction elements. Alpha-gustducin null mice have deficient GLP-1 secretion in response to glucose and show impaired regulation of plasma insulin and glucose after oral glucose. In the human L cell line NCI-H716, siRNA knockdown of alpha-gustducin blocked GLP-1 release stimulated by sugars and sucralose. Immunohistochemistry, RT-PCR (expression); alpha-gustducin KO mouse studies (in vivo glucose/GLP-1 measurements); ex vivo intestinal villi GLP-1 secretion assay; siRNA knockdown in NCI-H716 cells Proceedings of the National Academy of Sciences of the United States of America High 17724330
2007 T1R3 and alpha-gustducin expressed in enteroendocrine cells mediate intestinal sugar sensing and regulate SGLT1 mRNA and protein expression. Knockout mice lacking T1R3 or alpha-gustducin fail to upregulate SGLT1 expression or glucose absorptive capacity in response to dietary sugars or artificial sweeteners. Artificial sweeteners acting on GLUTag enteroendocrine cells stimulate gut hormones that upregulate SGLT1. T1R3 and alpha-gustducin knockout mice, SGLT1 mRNA and protein measurement (RT-PCR, Western blot), glucose absorption assays, GLUTag cell stimulation Proceedings of the National Academy of Sciences of the United States of America High 17724332
2008 Alpha-gustducin tonically maintains low basal cAMP levels in taste cells. In alpha-gustducin knockout mice, basal (unstimulated) cAMP is elevated compared to wild-type. Inhibition of cAMP-dependent protein kinase (PKA) with H-89 unmasks bitter responses in gustducin-lineage cells of knockout mice, indicating that elevated cAMP suppresses Ca2+ signaling needed for taste responses. cAMP measurement in taste buds (wild-type vs. alpha-gustducin KO), pharmacological PKA inhibition (H-89), calcium signaling recordings FEBS letters Medium 18930056
2011 Bitter taste receptors (T2R) and alpha-gustducin expressed in gastric ghrelin cells mediate ghrelin secretion in response to T2R agonists. Gavage of bitter T2R agonists increased plasma octanoyl ghrelin in wild-type but the effect was partially blunted in alpha-gustducin null mice. Alpha-gustducin-dependent ghrelin release then regulated food intake and hypothalamic AgRP expression. Alpha-gustducin KO mice, intragastric T2R agonist gavage, plasma ghrelin measurement by RIA, food intake measurement, hypothalamic AgRP mRNA quantification Proceedings of the National Academy of Sciences of the United States of America High 21245306
2013 Alpha-gustducin in colonic enteroendocrine cells couples fatty acid GPCRs (GPR40, GPR41, GPR43, GPR119, GPR120) and bile acid receptor TGR5 to GLP-1 secretion. Treatment of colonic mucosa with acetate, butyrate, oleic acid, oleoylethanolamide, or lithocholic acid stimulated GLP-1 secretion from wild-type but not alpha-gustducin knockout mice. Immunohistochemistry and co-localization (alpha-gustducin with fatty acid GPCRs in enteroendocrine cells), ex vivo colonic mucosa GLP-1 secretion assay with alpha-gustducin KO vs. wild-type mice American journal of physiology. Endocrinology and metabolism High 23341498
2018 Alpha-gustducin knockout mice develop aggravated DSS-induced colitis with increased weight loss, diarrhea, intestinal bleeding, inflammation, enhanced immune cell infiltration, increased TNF and IFN-γ, and decreased IL-13 and IL-5 expression in the colon. This establishes a role for alpha-gustducin in regulating gut mucosal immune balance. Alpha-gustducin KO mice in DSS-induced colitis model, histological scoring, immune cell infiltration analysis, cytokine mRNA quantification Brain, behavior, and immunity Medium 29678794
2020 GNAT3 (alpha-gustducin) expressed in metaplastic tuft cells (MTCs) suppresses pancreatic cancer progression by restraining CXCL1/CXCL2 secretion. Ablation of Gnat3 in oncogenic KRAS-expressing pancreatic organoids increased release of tumor-promoting cytokines CXCL1 and CXCL2. In vivo, Gnat3-null KRAS mice showed altered CXCR2+ MDSC populations with increased granulocytic MDSCs and faster progression to metastatic carcinoma. Gnat3-null mouse crossed with KC (KrasLSL-G12D/Ptf1aCre) and KCERT models; ex vivo organoid conditioned medium cytokine profiling; mass cytometry; single-cell RNA sequencing; survival/tumor progression analysis Cellular and molecular gastroenterology and hepatology High 32882403
2020 Alpha-gustducin in pancreatic beta-cells tonically suppresses basal cAMP, intracellular Ca2+, and insulin secretion independent of taste receptor signaling. siRNA knockdown of alpha-gustducin in INS-1 cells significantly elevated basal cAMP, intracellular calcium, and insulin secretion. siRNA knockdown of alpha-gustducin in INS-1 beta-cells, cAMP measurement, intracellular Ca2+ measurement, insulin secretion assay Journal of diabetes investigation Medium 31957256
2024 Alpha-gustducin (GNAT3) in gingival fibroblasts mediates anti-inflammatory bitter taste signaling via Tas2r143. Salicin activated Tas2r143, elicited taste signaling (calcium imaging confirmed), and inhibited LPS-induced CXCL1, CXCL2, and CXCL5 expression in mouse gingival fibroblasts. In Gnat3-/- mice, salicin failed to inhibit periodontal bone loss, inflammatory factors, and neutrophil infiltration, establishing GNAT3 as required for this anti-inflammatory pathway. Heterologous expression of taste receptor/Gα-gustducin + calcium imaging; RNA silence of Tas2r143; Gnat3-/- mouse periodontitis model (ligature-induced); qRT-PCR, immunofluorescence Frontiers in immunology High 38605968
2026 GNAT3 (alpha-gustducin) is specifically required for the anti-inflammatory effects of bitter T2R agonists (PTC, quinine, carisoprodol, chloroquine) in airway epithelial cells. siRNA-mediated GNAT3 knockdown significantly attenuated suppression of LPS-induced NF-κB activation (p-p65 and p-IκB phosphorylation) by all tested bitter agonists in BEAS-2B cells. siRNA knockdown of GNAT3 in BEAS-2B cells, Western blot for p65/p-p65 and IκB/p-IκB, qRT-PCR for IL-6 and IL-8, CCK-8 cytotoxicity assay International journal of molecular sciences Medium 41596643

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proceedings of the National Academy of Sciences of the United States of America 769 17724330
2007 T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proceedings of the National Academy of Sciences of the United States of America 675 17724332
1992 Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 518 1608467
1996 Transduction of bitter and sweet taste by gustducin. Nature 513 8657284
1996 Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proceedings of the National Academy of Sciences of the United States of America 317 8692869
1999 Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nature neuroscience 280 10570481
2011 Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proceedings of the National Academy of Sciences of the United States of America 262 21245306
2006 Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. American journal of physiology. Gastrointestinal and liver physiology 222 16728727
2006 Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and alpha-gustducin in the mammalian gut. American journal of physiology. Gastrointestinal and liver physiology 168 16710053
2003 Regional expression patterns of taste receptors and gustducin in the mouse tongue. Biochemical and biophysical research communications 124 14637165
2004 Umami taste responses are mediated by alpha-transducin and alpha-gustducin. The Journal of neuroscience : the official journal of the Society for Neuroscience 123 15342734
1997 Differential expression of alpha-gustducin in taste bud populations of the rat and hamster. The Journal of neuroscience : the official journal of the Society for Neuroscience 119 9092606
2000 Ultrastructural localization of gustducin immunoreactivity in microvilli of type II taste cells in the rat. The Journal of comparative neurology 115 10940948
1998 Identification of the taste cell G-protein, alpha-gustducin, in brush cells of the rat pancreatic duct system. Histochemistry and cell biology 103 9749964
2001 Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides. American journal of physiology. Cell physiology 102 11245589
2008 Colocalization of GPR120 with phospholipase-Cbeta2 and alpha-gustducin in the taste bud cells in mice. Neuroscience letters 82 19071193
2005 Contribution of alpha-gustducin to taste-guided licking responses of mice. Chemical senses 80 15800219
1998 Characterization and solubilization of bitter-responsive receptors that couple to gustducin. Proceedings of the National Academy of Sciences of the United States of America 77 9671782
2003 Behavioral evidence for a role of alpha-gustducin in glutamate taste. Chemical senses 71 14578119
2005 Co-expression patterns of the neuropeptides vasoactive intestinal peptide and cholecystokinin with the transduction molecules alpha-gustducin and T1R2 in rat taste receptor cells. Neuroscience 70 15561439
2003 Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 14586025
2007 A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells. Histochemistry and cell biology 66 17874119
2008 Tonic activity of Galpha-gustducin regulates taste cell responsivity. FEBS letters 65 18930056
2001 Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in alpha -gustducin. Proceedings of the National Academy of Sciences of the United States of America 56 11447270
2004 alpha-Gustducin immunoreactivity in the airways. Cell and tissue research 55 15654652
1999 Blocking taste receptor activation of gustducin inhibits gustatory responses to bitter compounds. Proceedings of the National Academy of Sciences of the United States of America 55 10449792
1998 The timing of alpha-gustducin expression during cell renewal in rat vallate taste buds. Chemical senses 54 9915120
1995 Functional expression of the taste specific G-protein, alpha-gustducin. The Biochemical journal 47 7626029
2002 Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin. Chemical senses 44 12379596
1994 Human taste cells express the G protein alpha-gustducin and neuron-specific enolase. Brain research. Molecular brain research 44 8015379
1999 alpha-Gustducin expression in the vomeronasal organ of the mouse. The European journal of neuroscience 39 10594676
2007 Expression of T1Rs and gustducin in palatal taste buds of mice. Chemical senses 38 17229761
2002 The neural differentiation gene Mash-1 has a distinct pattern of expression from the taste reception-related genes gustducin and T1R2 in the taste buds. Chemical senses 34 12052781
2023 Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis. Cell death & disease 32 36859525
2018 Aggravated gut inflammation in mice lacking the taste signaling protein α-gustducin. Brain, behavior, and immunity 32 29678794
2010 Enhanced expression of the sweet taste receptors and alpha-gustducin in reactive astrocytes of the rat hippocampus following ischemic injury. Neurochemical research 32 20596769
2020 The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice. Cellular and molecular gastroenterology and hepatology 31 32882403
2013 Gustducin couples fatty acid receptors to GLP-1 release in colon. American journal of physiology. Endocrinology and metabolism 31 23341498
2007 Expression of gustducin overlaps with that of type III IP3 receptor in taste buds of the rat soft palate. Chemical senses 31 17566068
2006 Expression of the G-protein alpha-subunit gustducin in mammalian spermatozoa. Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology 31 17021831
2008 Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin. Biochemical and biophysical research communications 28 18174025
2012 Metabolic syndrome is linked to chromosome 7q21 and associated with genetic variants in CD36 and GNAT3 in Mexican Americans. Obesity (Silver Spring, Md.) 27 22456541
1993 Gustducin and transducin: a tale of two G proteins. Ciba Foundation symposium 27 8168377
1999 Differential expression of carbohydrate blood-group antigens on rat taste-bud cells: relation to the functional marker alpha-gustducin. The Journal of comparative neurology 23 10545162
2011 Gα-gustducin is extensively coexpressed with sweet and bitter taste receptors in both the soft palate and fungiform papillae but has a different functional significance. Chemical senses 22 22016481
2000 Synaptic proteins in rat taste bud cells: appearance in the Golgi apparatus and relationship to alpha-gustducin and the Lewis(b) and A antigens. The Journal of comparative neurology 22 11054686
2015 Expression patterns of taste receptor type 1 subunit 3 and α-gustducin in the mouse testis during development. Acta histochemica 21 26589384
1998 Gustducin and its role in taste. Journal of dental research 20 9539456
2016 Distribution of α-Gustducin and Vimentin in premature and mature taste buds in chickens. Biochemical and biophysical research communications 19 27639649
2001 Differentiation of the lingual and palatal gustatory epithelium of the rat as revealed by immunohistochemistry of alpha-gustducin. Archives of histology and cytology 18 11757909
2010 Gustducin is expressed in the taste buds of the chicken. Animal science journal = Nihon chikusan Gakkaiho 17 21108686
2017 Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae. Neuroscience 16 29113930
2016 Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release. Molecular nutrition & food research 16 27800650
2008 Expression of alpha-gustducin in the circumvallate papillae of taste buds of diabetic rats. Acta histochemica 15 18824257
2003 Bovine circumvallate taste buds: taste cell structure and immunoreactivity to alpha-gustducin. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 15 12552638
2013 Effects of early intraoral acesulfame-K stimulation to mice on the adult's sweet preference and the expression of α-gustducin in fungiform papilla. Chemical senses 14 23537561
2018 Morphology of GNAT3-immunoreactive chemosensory cells in the rat larynx. Journal of anatomy 11 30467855
2006 Developmental change of alpha-gustducin expression in the mouse fungiform papilla. Anatomy and embryology 11 16933139
2006 Distribution of different taste buds and expression of alpha-gustducin in the barbells of yellow catfish (Pelteobagrus fulvidraco). Fish physiology and biochemistry 11 20035479
2014 Expression of α-gustducin and α-transducin, G proteins coupled with taste receptors, in boar sperm. Theriogenology 10 24751294
2008 Regional differences in taste bud distribution and alpha-gustducin expression patterns in the mouse fungiform papilla. Chemical senses 10 18296428
2021 Intestinal alteration of α-gustducin and sweet taste signaling pathway in metabolic diseases is partly rescued after weight loss and diabetes remission. American journal of physiology. Endocrinology and metabolism 9 34338041
2016 Regulation of α-Transducin and α-Gustducin Expression by a High Protein Diet in the Pig Gastrointestinal Tract. PloS one 9 26871573
2009 Genetically-increased taste cell population with G(alpha)-gustducin-coupled sweet receptors is associated with increase of gurmarin-sensitive taste nerve fibers in mice. BMC neuroscience 9 20028519
2024 Salicin alleviates periodontitis via Tas2r143/gustducin signaling in fibroblasts. Frontiers in immunology 8 38605968
1999 Cellular expression of alpha-gustducin and the A blood group antigen in rat fungiform taste buds cross-reinnervated by the IXth nerve. The Journal of comparative neurology 8 10363715
2007 Existence of subtypes of gustducin-immunoreactive cells in the vallate taste bud of guinea pigs. Archives of histology and cytology 7 18431029
2020 Characterization of the taste receptor-related G-protein, α-gustducin, in pancreatic β-cells. Journal of diabetes investigation 6 31957256
2019 Dietary Verbascoside Influences Gut Morphology and the Expression of α-Transducin and α-Gustducin in the Small Intestine of Weaned Piglets Exposed to n-6 Polyunsaturated Fatty Acids-Induced Oxidative Stress. Animals : an open access journal from MDPI 6 30634572
2016 Distribution of α-transducin and α-gustducin immunoreactive cells in the chicken (Gallus domesticus) gastrointestinal tract. Poultry science 5 26957624
2015 α-Transducin and α-gustducin immunoreactive cells in the stomach of common sole (Solea solea) fed with mussel meal. Fish physiology and biochemistry 5 25673424
2014 Non-specific immunostaining by a rabbit antibody against gustducin α subunit in mouse brain. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 5 25411190
2012 Chimeric yeast G-protein α subunit harboring a 37-residue C-terminal gustducin-specific sequence is functional in Saccharomyces cerevisiae. Bioscience, biotechnology, and biochemistry 5 22451393
2010 Gustation genetics: sweet gustducin! Chemical senses 5 20660058
2007 Differentiation of alpha-gustducin in taste buds of the mouse soft palate and fungiform papillae. Acta histochemica 5 17698174
2018 Enteroendocrine profile of α-transducin and α-gustducin immunoreactive cells in the chicken (Gallus domesticus) gastrointestinal tract. Poultry science 4 29955800
2011 Expression of α-gustducin in mammalian retinas. Neuroreport 4 21200350
2022 Worldwide diversity, association potential, and natural selection in the superimposed taste genes, CD36 and GNAT3. Chemical senses 3 34972209
2018 LPAR5, GNAT3 and partial amino acid transporters messenger RNA expression patterns in digestive tracts, metabolic organs and muscle tissues of growing goats. Animal : an international journal of animal bioscience 3 30378518
2006 Age-related expression of alpha-gustducin in the rat larynx. The Annals of otology, rhinology, and laryngology 3 16739672
2025 Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion. Acta pharmaceutica Sinica. B 2 41685140
2021 Morphology of GNAT3-immunoreactive chemosensory cells in the nasal cavity and pharynx of the rat. Journal of anatomy 2 33677835
2013 Occurrence of gustducin-immunoreactive cells in von Ebner's glands of guinea pigs. Histochemistry and cell biology 2 23604549
2011 Patterns of immunoreactivity specific for gustducin and for NCAM differ in developing rat circumvallate papillae and their taste buds. Acta histochemica 2 21703667
2010 Fixation conditions affect the immunoreactivity of gustducin in rat vallate taste buds. Archives of histology and cytology 2 21566335
2006 Structure of bovine fungiform taste buds and their immunoreactivity for gustducin. The Journal of veterinary medical science 2 17019065
2026 Defining the Critical Role of α-Gustducin for NF-κB Inhibition and Anti-Inflammatory Signal Transduction by Bitter Agonists in Lung Epithelium. International journal of molecular sciences 0 41596643

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