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Showing SLC6A11 — GAT3 is a alias.

SLC6A11

Sodium- and chloride-dependent GABA transporter 3 · UniProt P48066

Length
632 aa
Mass
70.6 kDa
Annotated
2026-06-10
58 papers in source corpus 21 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC6A11 (GAT3) is an astrocyte-localized, Na+- and Cl--dependent high-affinity GABA transporter that mediates glial GABA clearance and thereby sets ambient GABA tone to control neural circuit excitability (PMID:7935337, PMID:8815906, PMID:8738166). Transport requires more than one Na+ ion per cycle (sigmoidal Na+ dependence, Hill coefficient ~1.65) and a Cl- co-substrate whose binding precedes GABA recognition, and the transporter is pharmacologically distinguished from other GABA transporter subtypes by the selective inhibitor (S)-SNAP-5114 (PMID:7935337, PMID:7874447). Cryo-EM structures of the full-length human protein captured inhibitor-bound (inward-open), GABA-bound (inward-occluded), and substrate-free states, defining the ion-coordination network, a cation-π interaction between GABA's γ-amino group and a TM6 phenylalanine, and an intracellular inhibitor-binding pocket lined by TM1, 2, 3, 6, 7, and 8 (PMID:41611703). Surface delivery is directed by the C-terminal cytoplasmic tail, whose terminal THF motif mediates PDZ-dependent apical targeting (PMID:9748227). GAT3 membrane abundance is dynamically regulated: astrocyte Ca2+ entering through TRPA1 channels supports transport activity, while glutamate-receptor signaling, neuroinflammation, and substrate exposure adjust surface levels (PMID:22158513, PMID:25700791, PMID:27090509, PMID:29160736). Beyond reuptake, GAT3 can run in reverse to release GABA that drives tonic GABA-A and GABA-B receptor activation (PMID:24324407, PMID:37325697, PMID:16135550). Astrocytic GAT3 activity in the thalamus, pallidum, hippocampus, and cortex is required for normal circuit excitability, motor control, sensory encoding, and memory consolidation, and its enhancement protects against seizures after brain injury (PMID:35857628, PMID:29742425, PMID:39573851, PMID:42086667). Functionally validated loss-of-function SLC6A11 variants and haploinsufficiency reduce GABA uptake and cause genetic generalized epilepsy (PMID:39923323).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 High

    Establishing GAT3 as a functional, ion-coupled GABA transporter answered what activity the cloned gene product performs and how its transport cycle is energized.

    Evidence Heterologous expression in LLC-PK1 cells with radiolabeled GABA uptake, ion-substitution, and kinetic analysis

    PMID:7935337

    Open questions at the time
    • Stoichiometry inferred from Hill coefficients rather than direct ion flux measurement
    • Did not address native cellular context or trafficking
  2. 1994 High

    Identifying (S)-SNAP-5114 as a GAT3-preferring inhibitor distinguished GAT3 pharmacologically from GAT1, GAT2, and BGT1, providing the tool used in nearly all subsequent functional dissection.

    Evidence Molecular cloning, heterologous expression, and competitive uptake inhibition across four GABA transporter subtypes

    PMID:7874447

    Open questions at the time
    • Molecular basis of subtype selectivity not resolved
    • Did not define inhibitor binding site
  3. 1996 High

    Ultrastructural localization established that GAT3, unlike neuronal GAT1, resides in astrocytic processes, defining it as the glial arm of GABA uptake.

    Evidence Dual-label immunogold electron microscopy in rat cortex and cerebellum with subtype-specific antibodies

    PMID:8738166 PMID:8815906

    Open questions at the time
    • Did not establish functional consequence of glial localization
    • Mechanism restricting GABA spread inferred from anatomy
  4. 1998 High

    Mapping the apical-sorting signal to the C-terminal THF motif explained how GAT3 is targeted to a specific membrane domain and implicated a PDZ-domain partner.

    Evidence Deletion and chimeric GAT2/GAT3 constructs in polarized MDCK cells with immunofluorescence localization

    PMID:9748227

    Open questions at the time
    • The specific PDZ-domain protein was not identified
    • Sorting studied in epithelial, not astrocytic, cells
  5. 2005 Medium

    Showing that GAT3 blockade increases ambient GABA and IPSCs established that GAT3 actively limits extracellular GABA and shapes inhibitory output.

    Evidence Neocortical slice electrophysiology with SNAP-5114 and TTX action-potential controls

    PMID:16135550

    Open questions at the time
    • Did not distinguish uptake vs. carrier-mediated release directly
    • Single brain region, single lab
  6. 2011 High

    Linking astrocyte TRPA1-mediated Ca2+ microdomains to GAT3 function revealed that transport is dynamically gated by local astrocytic calcium.

    Evidence Membrane-tethered GCaMP3 imaging, TRPA1/GAT3 pharmacology, and slice electrophysiology

    PMID:22158513

    Open questions at the time
    • Molecular coupling between Ca2+ and transporter activity unresolved
    • Whether Ca2+ alters trafficking or intrinsic transport rate not separated
  7. 2011 Medium

    Demonstrating complementary phasic/tonic roles of glial GAT3 and axonal GAT1 in globus pallidus clarified the division of labor between the two transporters.

    Evidence Electron microscopic immunocytochemistry plus patch-clamp with selective GAT1/GAT3 blockers

    PMID:21410779

    Open questions at the time
    • Additive vs. interactive effects only inferred pharmacologically
    • Single lab
  8. 2013 Medium

    Identifying a reverse (releasing) mode of GAT3 contributing to tonic inhibition, lost in Huntington's models, extended GAT3's role beyond reuptake to active GABA supply.

    Evidence Patch-clamp in striatal slices with SNAP-5114 and TTX in two HD mouse models

    PMID:24324407

    Open questions at the time
    • Trigger and directionality control of reverse transport not defined
    • Single lab
  9. 2015 Medium

    Showing glutamate-receptor signaling reduces GAT3 surface levels identified neurotransmitter-driven trafficking as a regulator of glial GABA uptake capacity.

    Evidence Surface biotinylation and [3H]GABA uptake with receptor blockade in avian Muller glia

    PMID:25700791

    Open questions at the time
    • Signaling pathway downstream of glutamate receptors unknown (not PKC/PKA)
    • Avian retinal glia model
  10. 2016 Medium

    Demonstrating that neuroinflammation increases GAT3 membrane expression and elevates extracellular GABA tied transporter trafficking to disease-relevant behavioral deficits.

    Evidence Membrane Western blot, microdialysis, and behavior in hyperammonemic rats with sulforaphane rescue

    PMID:27090509

    Open questions at the time
    • Direct astrocyte signaling mediating increased surface GAT3 not defined
    • Single lab
  11. 2017 Medium

    Showing a GAT3 substrate (L-isoserine) can upregulate GAT3 and improve post-stroke recovery established substrate-induced trafficking as a tractable mechanism.

    Evidence Photothrombotic stroke model, Western blot, intracranial substrate infusion, and motor behavior

    PMID:29160736

    Open questions at the time
    • Trafficking mechanism inferred from expression changes, not directly imaged
    • Single lab
  12. 2018 Medium

    Linking pallidal GAT3 downregulation to elevated GABA tone and motor impairment in Parkinsonian models connected GAT3 directly to basal ganglia motor control.

    Evidence Western blot, slice patch-clamp, and in vivo GAT3 blockade in dopamine-depleted rodents

    PMID:29742425

    Open questions at the time
    • Cause of GAT3 downregulation after dopamine depletion unknown
    • Single lab
  13. 2022 High

    Bidirectional astrocyte-specific manipulation showed thalamic GAT3 level is causally sufficient to set circuit excitability and seizure risk, nominating it as a therapeutic target.

    Evidence Viral GAT3 knockdown/overexpression in thalamic astrocytes with EEG and seizure assays in injury models

    PMID:35857628

    Open questions at the time
    • Whether thalamic mechanism generalizes to other epileptogenic circuits unclear
    • Downstream receptor targets of altered GABA tone not mapped here
  14. 2024 Medium

    Identifying GAT3-driven Ca2+ entry via reverse Na+/Ca2+ exchange and its requirement for fear memory consolidation revealed a signaling output of GAT3 beyond GABA clearance.

    Evidence Patch-clamp, optogenetics, Ca2+ chelation, and contextual fear conditioning in dentate gyrus

    PMID:39573851

    Open questions at the time
    • Link between astrocytic Ca2+ and presynaptic GluN2B-NMDAR enhancement mechanistically incomplete
    • Single lab
  15. 2023 Medium

    Showing GAT3 reverse transport is the primary source of ambient GABA activating GABA-B receptors in developing cortex defined a developmental excitability-restraining role.

    Evidence Cortical slice patch-clamp and multi-electrode arrays with GAT3 and GABA-B blockade in GAD67-GFP mice

    PMID:37325697

    Open questions at the time
    • Developmental specificity vs. adult function not addressed
    • Single lab
  16. 2025 Medium

    Functional analysis of patient variants and modeled haploinsufficiency established a quantitative loss-of-function mechanism connecting reduced GAT3 GABA uptake to genetic generalized epilepsy.

    Evidence GABA uptake assays for SLC6A11 variants in HEK293T cells, cohort screening, EEG, and 4-PBA rescue

    PMID:39923323

    Open questions at the time
    • Causal proof in vivo from patient variants not yet shown
    • Genotype-phenotype severity correlation from preprint cohort (PMID-less) needs peer review
  17. 2026 High

    Cryo-EM of full-length human GAT3 in multiple states defined the atomic basis of GABA recognition, ion coordination, and inhibitor selectivity, anchoring decades of functional pharmacology to structure.

    Evidence Cryo-EM structures of wild-type human GAT3 bound to inhibitor, GABA, and substrate-free

    PMID:41611703

    Open questions at the time
    • Outward-facing and fully outward-open states not captured
    • Conformational dynamics of transport cycle inferred from static states
  18. 2026 Medium

    Showing hippocampal GAT3 inhibition selectively impairs memory consolidation via reduced protein synthesis distinguished a consolidation-specific role from general GABA transport.

    Evidence Stereotaxic SNAP-5114 injection, spatial object recognition, puromycin incorporation, and rescue experiments

    PMID:42086667

    Open questions at the time
    • Molecular path from GAT3 activity to protein synthesis not delineated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GAT3 surface trafficking, reverse-transport directionality, and astrocytic Ca2+ signaling are molecularly coordinated across circuits, and the identity of its PDZ-domain sorting partner, remain unresolved.
  • PDZ partner mediating THF-dependent targeting not identified
  • Mechanism switching uptake vs. release mode undefined
  • Direct in vivo causation for human epilepsy variants outstanding

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-382551 Transport of small molecules 2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2026 Cryo-EM structures of full-length wild-type human GAT3 were solved in three states: bound to a selective inhibitor (inward-open conformation), bound to substrate GABA (inward-occluded conformation), and substrate-free (inward-open). The inhibitor binds within the intracellular permeation pathway between transmembrane helices 1, 2, 3, 6, 7, and 8. GABA recognition involves a cation-π interaction between GABA's γ-amino group and a phenylalanine residue in transmembrane helix 6. The structures reveal the ion coordination network and the molecular determinants for inhibitor selectivity. Cryo-electron microscopy (cryo-EM) structural determination of full-length wild-type human GAT3 Nature communications High 41611703
1994 Human GAT3 was cloned and expressed, demonstrating high-affinity GABA transport (IC50 ~5 µM for (S)-SNAP-5114 inhibition). The transporter shows sigmoidal Na+ dependence (Hill coefficient ~1.65), indicating >1 Na+ ion per transport cycle, and hyperbolic Cl- dependence (Hill coefficient ~1.05, Km ~78 mM). Reduction in Cl- increases the apparent Km for GABA, suggesting Cl- interaction is an early step in the transport mechanism. β-alanine is both a substrate and competitive inhibitor. Stable expression in LLC-PK1 cells; radiolabeled GABA uptake assays; ion substitution experiments; pharmacological profiling Molecular pharmacology High 7935337
1994 Cloning and expression of the human homologue of GAT3 confirmed it as a functional GABA transporter. (S)-SNAP-5114 was identified as a selective inhibitor with IC50 of 5 µM at GAT3, 21 µM at GAT2, and ≥100 µM at GAT1 and BGT1, establishing GAT3 as a pharmacologically distinct transporter subtype. Molecular cloning; heterologous expression; competitive uptake inhibition assays Receptors & channels High 7874447
1998 Sorting determinants for GAT3 to the apical surface of polarized MDCK epithelial cells reside in its C-terminal cytoplasmic tail. A 22-amino-acid C-terminal sequence of GAT2 directs basolateral sorting; when appended to GAT3's C terminus, it redirects GAT3 to the basolateral surface. Deletion of 32 amino acids from GAT3's C terminus causes mislocalization to both surfaces. Removal of the final three amino acids (THF) of GAT3 disrupts apical sorting, suggesting interaction with a PDZ domain-containing protein mediates apical targeting. Stable expression of deletion constructs and chimeric GAT2/GAT3 transporters in MDCK cells; immunofluorescence localization assays The Journal of biological chemistry High 9748227
1996 GAT-3 immunoreactivity in adult rat cerebral cortex is localized exclusively to astrocytic processes (not neuronal cell bodies or axon terminals), including processes adjacent to both symmetric (GABAergic) and asymmetric synapses. Only some GAT-3-positive astrocytic processes are adjacent to GABAergic profiles, indicating GAT-3 mediates glial GABA uptake and may limit GABA spread beyond the synapse. Immunocytochemistry with affinity-purified antibodies; pre-embedding immunolabeling for GAT-3 combined with post-embedding immunogold labeling for GABA; electron microscopy The Journal of neuroscience High 8815906
1996 In rat cerebellum, GAT1 immunoreactivity is predominantly in presynaptic terminals whereas GAT3 immunoreactivity is localized to glial processes, as shown by electron microscopy. This establishes distinct cellular compartmentalization: neuronal GABA uptake via GAT1 and glial GABA uptake via GAT3. Immunoblot and immunocytochemistry with subtype-specific antibodies; electron microscopy Brain research. Molecular brain research High 8738166
2011 TRPA1 channel-mediated Ca2+ influx in astrocytes regulates GABA transport by GAT-3. Decreased astrocyte resting Ca2+ caused by TRPA1 inhibition reduces GABA transport by GAT-3, elevating extracellular GABA and reducing inhibitory synapse efficacy in hippocampal interneurons. Thus, TRPA1-generated Ca2+ microdomains near the plasma membrane target GAT-3 function in astrocytes. Membrane-tethered genetically encoded calcium indicator (Lck-GCaMP3) imaging; pharmacological blockade of TRPA1 and GAT-3 (SNAP-5114); electrophysiology in brain slices Nature neuroscience High 22158513
2013 In wild-type mouse striatum, GAT-3 operates in a releasing (reverse transport) mode, contributing to tonic GABAA receptor-mediated inhibition in striatal output neurons. In Huntington's disease mouse models (Z_Q175_KI and R6/2), this non-synaptic GABA release through GAT-3 is lost, reducing tonic inhibition. Astrocyte depolarization facilitates GABA release via GAT-3. Whole-cell patch-clamp recordings in acute brain slices; pharmacological blockade of GAT-3 with SNAP-5114; TTX application to separate synaptic from non-synaptic components Frontiers in neural circuits Medium 24324407
2018 In dopamine-depleted Parkinsonian rodents, glial GAT-3 transporters are downregulated in the external globus pallidus while neuronal GAT-1 function remains normal, leading to elevated extracellular GABA and persistent GABAergic tonic inhibition in GP neurons. In vivo GAT-3 blockade in control rodents impairs motor coordination, directly linking GAT-3 to basal ganglia motor control. Western blot for GAT-3 protein; whole-cell patch-clamp in brain slices; in vivo pharmacological blockade; dopamine depletion rodent models Cell reports Medium 29742425
2016 Neuroinflammation induced by hyperammonemia increases membrane expression of GAT-3 in activated astrocytes of the cerebellum, which increases extracellular GABA and impairs motor coordination and learning. Sulforaphane, by promoting M2 microglial polarization, reduces astrocyte activation and normalizes GAT-3 membrane expression and extracellular GABA levels. Western blot for GAT-3 membrane expression; immunohistochemistry; microdialysis for extracellular GABA; behavioral testing (Y maze, beam walking); sulforaphane treatment in hyperammonemic rats Journal of neuroinflammation Medium 27090509
2022 Down-regulation of GAT-3 in thalamic astrocytes is sufficient to produce cellular and circuit hyperexcitability, enhanced seizure risk, and cortical rhythm disruptions similar to those seen after cortical injury in mice. Enhancing GAT-3 expression specifically in thalamic astrocytes prevented these deficits and was protective against chemoconvulsant-induced seizures and mortality in a traumatic brain injury model. Viral vector-mediated GAT-3 knockdown and overexpression in thalamic astrocytes; EEG recording; seizure threshold testing; mouse models of cortical injury and TBI Science translational medicine High 35857628
2005 GAT-3 transporter blockade with SNAP-5114 in rat neocortical slices increases the amplitude of evoked GABAA responses and increases frequency and amplitude of spontaneous IPSCs in an action potential-dependent manner. This demonstrates that GAT-3 normally reduces ambient GABA levels, possibly by mediating carrier-mediated GABA release, and regulates inhibitory interneuron output. In vitro neocortical slice electrophysiology; pharmacological blockade of GAT-3 with SNAP-5114; TTX to test action potential dependence Journal of neurophysiology Medium 16135550
2011 In the rat globus pallidus, GAT-1 is localized preferentially to unmyelinated axons while GAT-3 is almost exclusively in glial processes. GAT-3 blockade (SNAP-5114) increases amplitude and prolongs decay time of evoked IPSCs from striatal stimulation, while GAT-1 blockade prolongs decay time only. Combined blockade has additive effects. High concentrations of both blockers induce GABAA receptor-mediated tonic currents, demonstrating complementary roles of the two transporters in regulating phasic and tonic inhibition. Electron microscopic immunocytochemistry; whole-cell patch-clamp in GP slices; pharmacological blockade with SKF89976A (GAT-1) and SNAP-5114 (GAT-3) The European journal of neuroscience Medium 21410779
2021 In the ventral pallidum, GAT-3 is upregulated in astrocytes during extinction of heroin seeking but not after mere withdrawal or extinction of sucrose seeking. Knockdown of GAT-3 with a vivo-morpholino restored heroin seeking in the extinguished context and disrupted extinction. This establishes that astrocytic GAT-3 upregulation is a necessary mechanism for extinction of drug seeking. Confocal microscopy with membrane-bound fluorescent labeling of astrocytes; Western blot for GAT-3; vivo-morpholino knockdown; heroin self-administration and extinction behavioral paradigm Molecular psychiatry Medium 34642457
2015 Glutamate activates ionotropic glutamate receptors on avian Müller glial cells to decrease GAT-3 plasma membrane levels (shown by surface biotinylation), reducing GABA uptake capacity by ~50%. This effect is not mediated by PKC or PKA signaling pathways. Conditioned media from retinal neurons also decreases GABA uptake in a glutamate receptor-dependent manner. Surface biotinylation assay; [3H]GABA uptake assay; pharmacological receptor blockade; conditioned media experiments Neurochemistry international Medium 25700791
2017 GAT3 protein levels are decreased in peri-infarct tissue from 6 hours to 42 days post-stroke in mice. The GAT3 substrate L-isoserine, administered into the infarct, increased GAT3 expression in peri-infarct regions and improved motor recovery in a concentration-dependent manner without affecting infarct volume, demonstrating that a GAT3 substrate can upregulate GAT3 surface expression as a substrate-induced trafficking mechanism. Photothrombotic stroke mouse model; Western blot for GAT3 protein; intracranial L-isoserine infusion; behavioral assessment (grid-walking, cylinder tasks); immunohistochemistry Journal of cerebral blood flow and metabolism Medium 29160736
2024 Activation of GAT-3 in dentate gyrus astrocytes triggers an increase in intracellular Ca2+ via the reverse Na+/Ca2+ exchanger. GAT-3 inhibition (SNAP-5114) impedes GABA-induced elevation of astrocytic Ca2+, curtailing subsequent enhancement of synaptic transmission. Endogenously released GABA from interneurons modulates synaptic transmission through GAT-3, and GAT-3 enhances excitatory transmission via presynaptic GluN2B-containing NMDARs. In vivo GAT-3 inhibition impairs contextual fear memory consolidation. Whole-cell patch-clamp; optogenetics; immunohistochemistry; behavioral assays (contextual fear conditioning); Ca2+ chelation experiments Glia Medium 39573851
2023 In developing somatosensory cortex of GAD67-GFP haplodeficient mice, GAT-3 operates in reverse (releasing) mode to provide ambient GABA for tonic activation of presynaptic and postsynaptic GABA-B receptors, restricting neuronal excitability. Blockade of GAT-3 (SNAP-5114) reproduced the effects of GABA-B receptor blockade (CGP55845), demonstrating that GAT-3-mediated reverse transport is the primary source of ambient GABA activating GABA-B receptors in this context. Whole-cell patch-clamp in cortical slices (P14-P21); multi-electrode array recordings; pharmacological blockade of GAT-3 and GABA-B receptors Frontiers in synaptic neuroscience Medium 37325697
2025 Haploinsufficiency of SLC6A11 (GAT3), as modeled in HEK293T cells, results in reduced GAT3 protein expression and reduced GABA uptake, comparable in magnitude to known SLC6A1 missense variants. This establishes that one functional allele of SLC6A11 is insufficient for normal GABA transport capacity. 4-phenylbutyrate (PBA) treatment improved GABA uptake in haploinsufficient models and reduced epileptiform discharges in patients. [3H]GABA uptake assays in HEK293T cells; Western blotting; EEG recordings in patients; clinical phenotyping Epilepsy research Medium 39923323
2025 Proteochemometric modeling identified amino acid Q299 (in GAT3, corresponding to L300/Q299/L294/L314 in GAT1/BGT1/GAT2/GAT3) as a key residue for ligand binding and subtype selectivity of GAT3 relative to the other GABA transporter subtypes. Proteochemometric modeling (partial least squares, random forest) using dataset of 323 compounds with bioactivity data across four GABA transporter subtypes; analysis of protein descriptor importance bioRxivpreprint Low
2025 Functionally validated SLC6A11 variants (identified in patients with genetic generalized epilepsy) show reduced GAT3 GABA uptake activity, and the degree of activity reduction is linked to epilepsy severity, establishing a quantitative loss-of-function mechanism for SLC6A11 variants in epilepsy. Functional GAT3 uptake assays for SLC6A11 variants; cohort screening of 708 epilepsy patients; correlation of functional activity with clinical severity bioRxivpreprint Medium
2024 Genetic ablation of GAT-3 (Gat3 CRISPR knockout) in astrocytes of the mouse visual cortex increases spontaneous and visually driven neuronal response magnitudes and trial-to-trial variability, and impairs population-level stimulus encoding, demonstrating that astrocytic GAT-3-mediated GABA clearance is required for accurate sensory information encoding. Multiplexed CRISPR/Cas9 Gat3 knockout in mouse visual cortex; in vivo two-photon calcium imaging; population neuronal response analysis bioRxivpreprint Medium
2026 GAT-3 inhibition with SNAP-5114 in the dorsal hippocampus impairs spatial memory consolidation (but not acquisition) and memory expression. This consolidation deficit is associated with reduced hippocampal protein synthesis (confirmed by puromycin incorporation assay). The memory deficit is rescued by prior open field exposure or proteasome inhibition but not by broader GABA transporter inhibition (nipecotic acid did not affect reconsolidation in the same way), indicating GAT-3 specifically modulates consolidation through protein synthesis mechanisms. Pharmacological GAT-3 inhibition (SNAP-5114) by stereotaxic injection; spatial object recognition task; puromycin incorporation assay for protein synthesis; behavioral rescue experiments Communications biology Medium 42086667
2025 In a C6 glioma model, GAT3 interacts with PMCA4 Ca2+ transporter and calmodulin within lipid raft microdomains. GAT3 knockdown alters resting Ca2+ and Ca2+ accumulation in lipid rafts following GABA stimulation, impairing glioma cell migration and invasion. Long-term GABA stimulation disrupts the PMCA4/GAT3 complex and induces GAT3- and CaMKII-dependent CREB phosphorylation at Ser133, controlling glioma invasiveness. Co-immunoprecipitation; lipid raft fractionation; Ca2+ imaging; GAT3 knockdown; glioma migration/invasion assays; Western blot for pCREB Cell calcium Low 40580687

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nature neuroscience 372 22158513
1996 GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and it is not confined to the vicinity of GABAergic synapses in the cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 225 8815906
1994 Production of specific antibodies against GABA transporter subtypes (GAT1, GAT2, GAT3) and their application to immunocytochemistry. Brain research. Molecular brain research 115 7854065
1996 Multiple gamma-Aminobutyric acid plasma membrane transporters (GAT-1, GAT-2, GAT-3) in the rat retina. The Journal of comparative neurology 99 8915826
2016 Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia. Journal of neuroinflammation 96 27090509
1994 Cloning of the human homologue of the GABA transporter GAT-3 and identification of a novel inhibitor with selectivity for this site. Receptors & channels 94 7874447
2013 Reduced tonic inhibition in striatal output neurons from Huntington mice due to loss of astrocytic GABA release through GAT-3. Frontiers in neural circuits 85 24324407
1998 Identification of sorting determinants in the C-terminal cytoplasmic tails of the gamma-aminobutyric acid transporters GAT-2 and GAT-3. The Journal of biological chemistry 79 9748227
2011 Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia. Frontiers in systems neuroscience 65 21847373
1996 Neuronal and glial localization of two GABA transporters (GAT1 and GAT3) in the rat cerebellum. Brain research. Molecular brain research 61 8738166
2006 GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus. Acta neuropathologica 54 16456667
1994 Stable expression of a neuronal gamma-aminobutyric acid transporter, GAT-3, in mammalian cells demonstrates unique pharmacological properties and ion dependence. Molecular pharmacology 52 7935337
2018 GAT-3 Dysfunction Generates Tonic Inhibition in External Globus Pallidus Neurons in Parkinsonian Rodents. Cell reports 50 29742425
2003 Postnatal development of high-affinity plasma membrane GABA transporters GAT-2 and GAT-3 in the rat cerebral cortex. Brain research. Developmental brain research 50 12694940
2003 Expression of GABA transporters, GAT-1 and GAT-3, in the cerebral cortex and thalamus of the rat during postnatal development. Cell and tissue research 49 12898208
2005 GAT-3 transporters regulate inhibition in the neocortex. Journal of neurophysiology 45 16135550
2001 Increased expression of gamma-aminobutyric acid transporters GAT-1 and GAT-3 in the spinal trigeminal nucleus after facial carrageenan injections. Pain 43 11323124
2022 Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents. Science translational medicine 38 35857628
2006 New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids. European journal of medicinal chemistry 35 16766089
2004 Changes in GABA transporters in the rat hippocampus after kainate-induced neuronal injury: decrease in GAT-1 and GAT-3 but upregulation of betaine/GABA transporter BGT-1. Journal of neuroscience research 35 15248296
2014 3p25.3 microdeletion of GABA transporters SLC6A1 and SLC6A11 results in intellectual disability, epilepsy and stereotypic behavior. American journal of medical genetics. Part A 33 25256099
2011 Differential localization and function of GABA transporters, GAT-1 and GAT-3, in the rat globus pallidus. The European journal of neuroscience 32 21410779
2005 Differential expression of the GABA transporters GAT-1 and GAT-3 in brains of rats, cats, monkeys and humans. Cell and tissue research 32 15821932
2018 Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus. Molecular brain 31 29370841
2015 Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3. ACS chemical neuroscience 30 26154082
2021 Astrocytes in the ventral pallidum extinguish heroin seeking through GAT-3 upregulation and morphological plasticity at D1-MSN terminals. Molecular psychiatry 29 34642457
2009 Reduced expression of GABA transporter GAT3 in helpless rats, an animal model of depression. Neurochemical research 27 19288275
1998 Developmental expression of gamma-aminobutyric acid transporters (GAT-1 and GAT-3) in the rat cerebellum: evidence for a transient presence of GAT-1 in Purkinje cells. Brain research. Developmental brain research 26 9838150
2021 Baclofen decreases compulsive alcohol drinking in rats characterized by reduced levels of GAT-3 in the central amygdala. Addiction biology 25 33527681
2003 Transient focal ischemia triggers neuronal expression of GAT-3 in the rat perilesional cortex. Neurobiology of disease 25 13678673
2021 Downregulation of GABA Transporter 3 (GAT3) is Associated with Deficient Oxidative GABA Metabolism in Human Induced Pluripotent Stem Cell-Derived Astrocytes in Alzheimer's Disease. Neurochemical research 23 33710537
1999 Developmental expression of the neurotransmitter transporter GAT3. Journal of neuroscience research 23 10348670
2017 GAT3 selective substrate l-isoserine upregulates GAT3 expression and increases functional recovery after a focal ischemic stroke in mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 22 29160736
2014 Functional analysis of the inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 in astrocytes of the lateral superior olive. Glia 21 25103283
2000 A light and electron microscopic study of the GABA transporter GAT-3 in the monkey basal ganglia and brainstem. Journal of neurocytology 21 11283414
2005 Neuronal localization of the GABA transporter GAT-3 in human cerebral cortex: a procedural artifact? Journal of chemical neuroanatomy 20 15923108
1999 Expression of GABA transporter subtypes (GAT1, GAT3) in the adult rabbit retina. Acta ophthalmologica Scandinavica 19 10406141
2015 Functional plasticity of GAT-3 in avian Müller cells is regulated by neurons via a glutamatergic input. Neurochemistry international 17 25700791
2013 Gaba transporter SLC6A11 gene polymorphism associated with tardive dyskinesia. Nordic journal of psychiatry 16 23795861
2020 GAT-1 (rs2697153) and GAT-3 (rs2272400) polymorphisms are associated with febrile seizures and temporal lobe epilepsy. Epileptic disorders : international epilepsy journal with videotape 14 32301730
2011 Association of a synonymous GAT3 polymorphism with antiepileptic drug pharmacoresistance. Journal of human genetics 10 21776001
1999 Immunoreactivity for multiple GABA transporters (GAT-1, GAT-2, GAT-3) in the gerbil pineal gland. Neuroscience letters 10 10353341
1998 Increased expression of GABA transporters, GAT-1 and GAT-3, in the deafferented superior colliculus of the rat. Brain research 10 9479049
2025 4-Phenylbutyrate restored GABA uptake, mitigated seizures in SLC6A1 and SLC6A11 microdeletions/3p- syndrome: From cellular models to human patients. Epilepsy research 9 39923323
2001 Developmental changes in GABA transporter (GAT1 and GAT3) mRNA expressions in the rat olfactory bulb. Brain research. Developmental brain research 9 11248347
1999 Quantitation of GABA transporter 3 (GAT3) mRNA in rat brain by competitive RT-PCR. Brain research. Brain research protocols 7 10592344
2023 Tonic activation of GABAB receptors via GAT-3 mediated GABA release reduces network activity in the developing somatosensory cortex in GAD67-GFP mice. Frontiers in synaptic neuroscience 6 37325697
1999 Expression of GABA transporter subtypes (GAT1, GAT3) in the developing rabbit retina. Acta ophthalmologica Scandinavica 6 10406142
2024 Astrocytic GAT-3 Regulates Synaptic Transmission and Memory Formation in the Dentate Gyrus. Glia 5 39573851
2012 Development and validation of an LC-ESI-MS/MS quantification method for a potential γ-aminobutyric acid transporter 3 (GAT3) marker and its application in preliminary MS binding assays. Biomedical chromatography : BMC 3 23225341
2024 Manganese- and zinc-coordinated interaction of Schistosoma japonicum glutathione S-transferase with neurotransmitter transporters GlyT1 and GAT3 in vitro. Experimental parasitology 2 38369179
2017 Lack of Association between SLC6A11 Genetic Polymorphisms and Drug Resistant Epilepsy in Chinese Han Population. Clinical laboratory 2 28792706
2026 Structural basis for selective inhibition of human GABA transporter GAT3. Nature communications 0 41611703
2026 Prelimbic cortex to zona incerta pathway mediates recognition memory recovery delay through down-regulating astrocytic GAT-3. iScience 0 41797906
2026 Hippocampal astrocytic GAT-3 blockade impairs protein synthesis and spatial memory dynamics. Communications biology 0 42086667
2025 GAT3-dependent regulation of glioma invasiveness via a lipid raft-associated PMCA4 Ca2+ transporter and a downstream CaMKII/CREB signaling - implications for compartmentalized signaling in glioma tumors. Cell calcium 0 40580687
2025 Association of CYP3A4*1B and SLC6A11 Genetic Variants with Epilepsy Risk And Antiepileptic Drug Response in an Iraqi Population. Molecular neurobiology 0 41410815
2003 [Changes in GAT-3 and GABA-T mRNA expression of C6 glioma cells in response to a 2-week treatment with sodium valproate and withdrawal]. Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA 0 13129709

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