Affinage

SLC30A3

Probable proton-coupled zinc antiporter SLC30A3 · UniProt Q99726

Length
388 aa
Mass
41.9 kDa
Annotated
2026-06-10
56 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC30A3/ZnT3 is a six-transmembrane H+/Zn2+ antiporter that is the essential, rate-limiting transporter for loading zinc into synaptic vesicles of glutamatergic neurons (PMID:8962159, PMID:9990090). It decorates the membranes of clear small round synaptic vesicles in hippocampal mossy fiber boutons (PMID:9356509), and its targeting to this distinct synaptic-vesicle subpopulation depends on a selective interaction between its cytosolic tail and the AP-3 adaptor complex (PMID:14657250). ZnT3 controls the total elemental zinc mass of mossy fiber vesicles, and genetic disruption abolishes histochemically reactive vesicular zinc throughout the brain in a gene-dosage-dependent manner (PMID:9990090, PMID:19521526). Its transport and vesicular targeting are regulated by covalent dityrosine-mediated homo-oligomerization at residues Y357 and Y372, which is enhanced by oxidative stress (PMID:19521526), and a high-affinity N-terminal -HHCH- zinc-binding site supports zinc sensing or translocation (PMID:23839275); cryo-EM of the human protein in an inward-facing state defines the conformational basis of its H+/Zn2+ antiport cycle (PMID:39474773). Functionally, ZnT3 couples to the vesicular glutamate transporter Vglut1 to co-regulate neurotransmitter content (PMID:15860731) and is required for activity-dependent presynaptic Erk1/2 MAPK signaling underlying hippocampus-dependent memory (PMID:21245308). Beyond the synapse, ZnT3 governs zinc handling in pancreatic beta-cell insulin granules (PMID:19492079, PMID:26867900) and oocytes (PMID:39048372), and drives pathological extracellular zinc release during cerebral ischemia, where vesicular zinc activates MMP-2 to degrade tight junctions and disrupt the blood-brain barrier, a process involving physical interaction with TMEM163 (PMID:37962463, PMID:41504061). Its expression is transcriptionally activated by Sp1 (displaced by mutant huntingtin) and epigenetically repressed by HDAC1-mediated H3K27ac deacetylation (PMID:32944220, PMID:33715270).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 Medium

    Established the molecular identity of the synaptic vesicle zinc transporter, answering whether a dedicated protein accounts for the long-observed histochemical pool of synaptic zinc.

    Evidence Homology cloning, expression profiling, and C-terminal-antibody immunohistochemistry matching Timm's stain

    PMID:8962159

    Open questions at the time
    • Transport function inferred from localization, not measured directly
    • Topology of the six predicted TM domains not experimentally confirmed
  2. 1997 High

    Resolved the precise subcellular site of ZnT-3 action, showing it resides on the membranes of zinc-containing small clear synaptic vesicles.

    Evidence Immunogold electron microscopy and Timm's staining in mouse and monkey hippocampus

    PMID:9356509

    Open questions at the time
    • Does not establish directionality or proton dependence of transport
    • Did not address what loads zinc into vesicles biochemically
  3. 1999 High

    Provided genetic proof that ZnT3 is required and rate-limiting for vesicular zinc accumulation in vivo, converting a localization-based hypothesis into causal necessity.

    Evidence Targeted ZnT3 knockout mice with Timm's staining and zinc quantification, including heterozygote dose-response

    PMID:9990090

    Open questions at the time
    • Residual ~80% of total brain zinc is ZnT3-independent and unexplained
    • Did not resolve transport stoichiometry or mechanism
  4. 2000 High

    Separated synaptic vesicular zinc from the toxic intraneuronal zinc of neurodegeneration, refining the disease relevance of the ZnT3 pool.

    Evidence ZnT3 knockout mice in a kainate seizure model with zinc dyes and CaEDTA rescue

    PMID:10807937

    Open questions at the time
    • Source of the toxic non-vesicular zinc not identified here
    • Did not address ischemic versus excitotoxic contexts
  5. 2003 High

    Defined the trafficking route that delivers ZnT3 to synaptic vesicles, identifying AP-3 as the adaptor and revealing molecular heterogeneity among synaptic vesicles.

    Evidence Cell-free cytosolic tail–AP-3 binding assays, AP-3-null mocha brain analysis, and SV immunoisolation

    PMID:14657250

    Open questions at the time
    • Precise tail motif binding AP-3 not mapped
    • How the AP-3 pathway determines functional SV identity remains open
  6. 2005 High

    Showed that ZnT3 transport is functionally coupled to glutamate loading, establishing that vesicular zinc and neurotransmitter content are co-regulated.

    Evidence Deconvolution microscopy, fractionation, and flow-cytometry zinc-uptake assays in PC12 cells co-expressing ZnT3 and Vglut1

    PMID:15860731

    Open questions at the time
    • Molecular basis of the bidirectional coupling unresolved
    • Whether ZnT3 and Vglut1 physically associate not shown
  7. 2007 High

    Demonstrated ZnT3 controls total elemental zinc mass, not merely the histochemically reactive fraction, quantifying its transport output.

    Evidence Synchrotron X-ray fluorescence microprobe on ZnT3 knockout versus wild-type brain

    PMID:17712179

    Open questions at the time
    • Does not address dynamic flux or transport kinetics
    • Other zinc transporters' contribution not quantified
  8. 2009 High

    Identified a covalent oligomerization mechanism regulating ZnT3 targeting and transport capacity, linking redox state to zinc loading.

    Evidence Site-directed mutagenesis (Y357F, Y372F) with oligomer, SLMV targeting, and zinc-toxicity readouts in PC12 cells

    PMID:19521526

    Open questions at the time
    • In vivo relevance of dityrosine dimers not demonstrated
    • Enzymatic basis of dityrosine formation unknown
  9. 2009 Medium

    Extended ZnT3 function to non-neuronal endocrine zinc handling, implicating it in insulin production and glucose homeostasis.

    Evidence siRNA knockdown in INS-1E beta cells and streptozotocin-stressed ZnT3 knockout mice

    PMID:19492079

    Open questions at the time
    • Mechanistic link between vesicular zinc and insulin synthesis unclear
    • Relationship to other beta-cell zinc transporters not addressed here
  10. 2011 High

    Placed ZnT3-dependent vesicular zinc upstream of presynaptic Erk1/2 MAPK signaling required for memory, defining a signaling output of synaptic zinc.

    Evidence ZnT3 knockout mice with Erk1/2 and phosphatase assays, behavioral tests, and pharmacological blockade

    PMID:21245308

    Open questions at the time
    • Identity of the zinc-sensitive MAPK phosphatase not defined
    • Direct molecular zinc target at the synapse unknown
  11. 2013 Medium

    Characterized the high-affinity N-terminal zinc-binding determinant, distinguishing it from the His-rich intracellular loop and implicating it in sensing or translocation.

    Evidence Potentiometric and spectroscopic analysis of synthetic peptides modeling ZnT3 metal-binding sequences

    PMID:23839275

    Open questions at the time
    • Peptide models, not intact protein
    • Functional role of the site in transport not tested in cells
  12. 2016 Medium

    Revealed ZnT3 as an ERK-coupled cytoprotective and tumor-suppressive factor outside neurons, and identified epigenetic and transcriptional control of its expression.

    Evidence siRNA knockdown in SH-SY5Y/HEK293 under ER stress, ChIP-seq and HDAC1 manipulation in glioblastoma, and beta-cell immunogold/expression studies

    PMID:26867900 PMID:27678294 PMID:33715270

    Open questions at the time
    • How a synaptic zinc transporter activates MAPK in these contexts mechanistically unclear
    • Direct versus indirect effects on ERK not separated
  13. 2020 Medium

    Mapped transcriptional and post-transcriptional regulators of ZnT3, linking its loss to disease states via Sp1 displacement by mutant huntingtin and miR-5572.

    Evidence Luciferase reporter, ChIP, and Sp1 rescue in HD models; miRNA profiling and target validation in ALS spinal cord

    PMID:32599739 PMID:32944220

    Open questions at the time
    • miR-5572 finding is single-study and low confidence
    • Whether ZnT3 loss is causal or correlative in these neurodegenerations not established
  14. 2023 High

    Established a pathological efflux role: neuronal ZnT3-derived extracellular zinc activates MMP-2 to degrade tight junctions and disrupt the blood-brain barrier in ischemia.

    Evidence Neuronal-specific ZnT3 knockout mice and rat stroke model with ECF-zinc, MMP-2 activity, tight junction, and BBB permeability assays

    PMID:37962463

    Open questions at the time
    • How synaptic vesicle zinc reaches the extracellular space mechanistically not fully resolved
    • Whether MMP-2 activation is direct zinc binding versus indirect not definitively separated
  15. 2024 High

    Determined the human ZnT3 structure, providing a conformational framework for the H+/Zn2+ antiport mechanism.

    Evidence Cryo-EM of inward-facing human ZnT3 compared with outward-facing ZnT4

    PMID:39474773

    Open questions at the time
    • Zinc-bound and proton-coupled intermediate states not captured
    • Structural basis of dityrosine oligomerization not resolved
  16. 2024 Medium

    Broadened ZnT3 physiology, linking it to neural progenitor zinc homeostasis via WFS1, to dendritic/insulin-signaling architecture in hippocampus, and to oocyte zinc accumulation.

    Evidence WFS1 knockout mice and cerebral organoids with riluzole; ZnT3 knockout Golgi-Cox and synaptosome analyses; ZnT3 knockout oocyte zinc measurement

    PMID:38807922 PMID:39048372 PMID:39258564

    Open questions at the time
    • Whether WFS1 regulates ZnT3 directly or via lipid metabolism unclear
    • Reproductive consequence of oocyte zinc loss is absent (normal fertility)
  17. 2025 Medium

    Identified TMEM163 as a physical partner cooperating with ZnT3 in ischemia-induced neuronal zinc efflux, refining the efflux mechanism.

    Evidence Co-immunoprecipitation, surface biotinylation, siRNA/overexpression, and zinc/apoptosis assays under oxygen-glucose deprivation

    PMID:41504061

    Open questions at the time
    • Single Co-IP without reciprocal endogenous validation
    • Stoichiometry and functional consequence of the ZnT3-TMEM163 complex unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZnT3 mechanistically couples vesicular zinc loading to downstream MAPK signaling, and how it transitions from a vesicle-loading transporter to a driver of pathological extracellular efflux, remain unresolved.
  • No direct molecular zinc sensor connecting ZnT3 to ERK identified
  • Mechanism redirecting vesicular zinc to extracellular space during ischemia incompletely defined
  • Zinc-bound transport intermediate structures not yet captured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140104 molecular carrier activity 3
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
AP-3MMP-2SLC17A7SP1TMEM163WFS1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ZnT-3 (SLC30A3) was cloned and identified as a membrane protein with six predicted transmembrane domains, expressed restrictively in brain and testis. Antibodies against the C-terminal tail produced a staining pattern matching Timm's stain for synaptic vesicle zinc, leading to the proposal that ZnT-3 facilitates zinc accumulation in synaptic vesicles. Homology cloning, Northern blot, RT-PCR, in situ hybridization, immunohistochemistry with C-terminal antibody Proceedings of the National Academy of Sciences of the United States of America Medium 8962159
1997 ZnT-3 protein localizes to the membranes of all clear small round synaptic vesicles (SVs) in mossy fiber boutons of mouse and monkey hippocampus, as shown by electron microscopy; up to 60-80% of these ZnT-3-decorated SVs contain Timm's-stainable zinc, establishing ZnT-3 as the transporter responsible for zinc accumulation in SVs. Electron microscopy immunogold localization, Timm's staining Proceedings of the National Academy of Sciences of the United States of America High 9356509
1999 ZnT3 is required for transport of zinc into synaptic vesicles in vivo: targeted disruption of the ZnT3 gene completely eliminated histochemically reactive zinc from synaptic vesicles throughout the brain, reduced total hippocampal/cortical zinc by ~20%, and showed that vesicular zinc concentration is determined by ZnT3 protein abundance (heterozygotes have intermediate zinc). Targeted gene disruption (ZnT3 knockout mice), Timm's staining, zinc quantification Proceedings of the National Academy of Sciences of the United States of America High 9990090
2000 ZnT3 knockout mice completely lack histochemically reactive synaptic vesicle zinc but still accumulate intraneuronal zinc after kainate seizures, establishing that the source of toxic zinc accumulation in neurodegeneration is NOT synaptic vesicles but other extracellular sources. ZnT3 knockout mice, kainate seizure model, zinc-specific fluorescent dye (MQAE/TSQ) staining, CaEDTA injection The Journal of neuroscience : the official journal of the Society for Neuroscience High 10807937
2003 ZnT3 cytosolic tail interacts selectively with the AP-3 adaptor complex (not AP-2), and ZnT3 is preferentially targeted to a distinct AP-3-dependent subpopulation of synaptic vesicles; in AP-3-deficient (mocha) neurons, ZnT3 content in SVs is reduced while synaptophysin is unaffected, demonstrating molecularly heterogeneous SV populations. Cell-free binding assays (cytosolic tail–AP-3 interaction), pharmacological disruption of AP-2/AP-3 pathways, immunoisolation of SV subpopulations, analysis of AP-3-deficient mocha brain Molecular biology of the cell High 14657250
2005 ZnT3 and the vesicular glutamate transporter Vglut1 co-localize on the same synaptic vesicles in PC12 cells and brain; Vglut1 expression increases vesicular zinc uptake by ZnT3, and ZnT3 expression increases vesicular glutamate uptake in a zinc-dependent manner, demonstrating that the coupling of ZnT3 and Vglut1 transport mechanisms regulates neurotransmitter content in secretory vesicles. Deconvolution microscopy, subcellular fractionation, whole-cell flow cytometry zinc uptake assay, PC12 cell lines overexpressing ZnT3 and/or Vglut1 Journal of cell science High 15860731
2007 ZnT3 (encoded by Slc30a3) controls the total elemental mass of zinc in hippocampal mossy fiber synaptic vesicles, not only the histochemically reactive pool; synchrotron X-ray fluorescence microprobe shows the normal 2-3 fold zinc elevation in mossy fibers is absent in ZnT3 knockout mice. Microprobe synchrotron X-ray fluorescence (SRXRF) on ZnT3 knockout mouse brain sections The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society High 17712179
2009 ZnT3 undergoes covalent homo-oligomerization via intermolecular dityrosine bonds; Y372 and Y357 are the critical residues forming the predominant dimer. Y372F mutation prevents oligomerization, reduces ZnT3 targeting to synaptic-like microvesicles (SLMVs), and decreases zinc transport/resistance to zinc toxicity. Y357F is a gain-of-function mutation with increased oligomerization, SLMV targeting, and zinc transport capacity. Oxidative stress enhances dityrosine dimerization. Site-directed mutagenesis of tyrosine residues, expression in PC12 cells, biochemical analysis of oligomeric species, zinc toxicity assay, SLMV targeting assay PloS one High 19521526
2009 ZnT3 knockdown by siRNA in INS-1E pancreatic beta cells decreases insulin expression and secretion; ZnT3 knockout mice show higher blood glucose after streptozotocin-induced beta cell stress, demonstrating a role for ZnT3 in insulin production and glucose metabolism in beta cells. siRNA knockdown in INS-1E cells, insulin secretion assay, ZnT3 knockout mice with streptozotocin treatment, glucose measurement PloS one Medium 19492079
2011 ZnT3 is required for presynaptic Erk1/2 MAPK signaling in hippocampal mossy fiber terminals; ZnT3 knockout mice show reduced Erk1/2 activation, disinhibition of zinc-sensitive MAPK tyrosine phosphatase activity, impaired MAPK signaling during learning, and complete deficits in contextual discrimination and spatial working memory. Activity-dependent exocytosis is required for the effect of vesicular zinc on presynaptic MAPK and phosphatase activity. ZnT3 knockout mice, biochemical analysis of Erk1/2 phosphorylation, phosphatase activity assays, behavioral tests (contextual discrimination, spatial working memory), pharmacological blockade of zinc or MAPK in mossy fiber pathway Proceedings of the National Academy of Sciences of the United States of America High 21245308
2012 ZnT3 downregulation in vascular smooth muscle cells (VSMCs) mediates Angiotensin II-induced cellular senescence; ZnT3 overexpression decreases ROS and prevents senescence. ZnT3 downregulation reduces catalase expression via decreased ERK1/2 phosphorylation (post-transcriptional mechanism), elevating ROS and promoting senescence. siRNA knockdown and overexpression of ZnT3 in VSMCs, ROS measurement, NADPH oxidase activity assay, Akt activation assay, catalase expression analysis, senescence assays PloS one Medium 22427991
2013 The conserved N-terminal -HHCH- sequence (modeled by peptide L3: Ac-PFHHCHRD-NH2) is a high-affinity zinc-binding site in human ZnT3, with 3-4 orders of magnitude higher zinc stability than the His-rich intracellular loop; the N-terminal site shows preferred zinc binding over nickel, suggesting a role in zinc sensing or translocation. Potentiometric and solution structural analysis (UV-Vis, CD, EPR, NMR) of synthetic peptides mimicking ZnT3 metal-binding sequences Dalton transactions (Cambridge, England : 2003) Medium 23839275
2016 SLC30A3 expression is epigenetically repressed in glioblastoma by HDAC1-mediated deacetylation of histone H3K27ac at the super enhancer region of the SLC30A3 locus; SLC30A3 overexpression inhibits GBM cell growth and metastasis and activates the MAPK signaling pathway to promote apoptosis. ChIP-seq, HDAC1 overexpression/knockdown, functional cell growth/invasion assays in vitro and in vivo, MAPK pathway analysis IUBMB life Medium 33715270
2016 SLC30A3 protects cells from ER stress-induced toxicity via ERK1/2 activation; SLC30A3 knockdown prevents tunicamycin-induced ERK1/2 phosphorylation, increases cleaved caspase-3, and reduces cell viability under ER stress conditions. siRNA knockdown of SLC30A3 in SH-SY5Y and HEK293 cells, tunicamycin-induced ER stress, ERK1/2 phosphorylation assay, caspase-3 cleavage, cell viability assay Biochemical and biophysical research communications Medium 27678294
2016 In INS-1E pancreatic beta cells, ZnT3 localizes to insulin-containing granules near the plasma membrane (immuno-gold EM); ZnT3 overexpression decreases ZnT8 mRNA, decreases insulin content and secretion, but improves cell survival; ZnT3 and ZnT8 expression are inversely correlated, suggesting transcriptional co-regulation. Immuno-gold electron microscopy, ZnT3 overexpression, insulin content/secretion assay, qPCR for ZnT8 mRNA, cell survival assay Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine Medium 26867900
2020 Mutant huntingtin inhibits the binding of transcription factor Sp1 to GC boxes in the ZnT3 promoter, downregulating ZnT3 expression and depleting synaptic vesicular zinc in hippocampus, cortex, and striatum of HD transgenic mice; Sp1 overexpression rescues ZnT3 expression. Dual-luciferase reporter gene assay, chromatin immunoprecipitation (ChIP), Western blot, RT-PCR, immunohistochemistry, autometallography in N171-82Q HD transgenic mice and BHK cells expressing mutant huntingtin Cell & bioscience Medium 32944220
2020 miR-5572 directly regulates SLC30A3 expression in spinal cord; miR-5572 levels are elevated in sporadic ALS spinal cords, and SLC30A3 was validated as a target gene of miR-5572. Microarray and RT-PCR for miRNA profiling, TargetScan prediction, experimental validation of miR-5572 regulation of SLC30A3 International journal of molecular sciences Low 32599739
2023 Neuronal ZnT3 is the source of elevated extracellular free zinc (ECF-Zn) following cerebral ischemia; neuronal-specific ZnT3 knockout markedly reduces ECF-Zn and blood-brain barrier (BBB) permeability after ischemia. Elevated ECF-Zn directly binds to MMP-2 in extracellular fluid, increases its zinc content, augments MMP-2 activity, degrades tight junction proteins in cerebral microvessels, and disrupts the BBB. Neuronal-specific ZnT3 knockout mice, rat stroke model, ECF zinc measurement, MMP-2 activity assay, tight junction protein analysis, BBB permeability assay Aging and disease High 37962463
2024 Cryo-EM structures of human ZnT3 (inward-facing conformation) and ZnT4 (outward-facing) were determined; combining these structures revealed the conformational changes in the transmembrane domain during H+/Zn2+ antiport transport, providing a structural basis for the Zn2+ transport mechanism of ZnT3. Cryo-electron microscopy, structural comparison of inward- and outward-facing conformations FEBS letters High 39474773
2024 WFS1 regulates Zn2+ homeostasis in neural progenitor cells (NPCs) by inhibiting ZnT3 under dysregulated lipid metabolism conditions; WFS1 deficiency leads to increased ZnT3 activity, zinc dyshomeostasis, and apoptosis of NPCs and cerebral organoids. Riluzole regulates ZnT3 expression to maintain zinc homeostasis and protect NPCs from lipotoxicity. Neural-specific WFS1 knockout mice, hESC neural differentiation, cerebral organoids, riluzole treatment, apoptosis assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39258564
2024 ZnT3 knockout in mice decreases hippocampal/cortical zinc, increases dendritic complexity, decreases mature dendritic spine density, and reduces expression of GLUT3, GLUT4, insulin receptor, AKT, and insulin-induced AKT phosphorylation in hippocampal synaptosome fractions, linking ZnT3 to synaptic plasticity and insulin/glucose metabolism signaling. ZnT3 knockout mice, Golgi-Cox staining (dendritic analysis), Western blot for glucose transporters and insulin signaling components in hippocampal synaptosome fractions, zinc quantification Frontiers in molecular neuroscience Medium 38807922
2024 ZnT3 plays a role in zinc ion influx/accumulation in mouse oocytes; ZnT3 KO mice have significantly reduced intracellular zinc ions in oocytes/zygotes and lack free zinc accumulation in the oocyte cytoplasm, though fertilization rates and litter sizes are normal. ZnT3 knockout mice, intracellular zinc measurement in oocytes/zygotes, fertilization and litter size analysis The Journal of reproduction and development Medium 39048372
2025 ZnT3 and TMEM163 physically interact (co-immunoprecipitation) and cooperatively regulate zinc efflux from hippocampal neurons; oxygen-glucose deprivation (OGD) causes both proteins to translocate from the cell membrane to the cytoplasm, leading to extracellular zinc overload and neuronal apoptosis. Overexpression exacerbates zinc efflux and damage; silencing attenuates zinc overload and neurodegeneration. Co-immunoprecipitation, cell surface biotinylation/subcellular localization, siRNA silencing and plasmid overexpression, MTT assay, TUNEL staining, FluoZin-3 zinc fluorescence, ELISA for extracellular zinc Frontiers in bioscience (Landmark edition) Medium 41504061

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 ZnT-3, a putative transporter of zinc into synaptic vesicles. Proceedings of the National Academy of Sciences of the United States of America 590 8962159
1999 Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proceedings of the National Academy of Sciences of the United States of America 457 9990090
1997 Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey. Proceedings of the National Academy of Sciences of the United States of America 302 9356509
2000 Accumulation of zinc in degenerating hippocampal neurons of ZnT3-null mice after seizures: evidence against synaptic vesicle origin. The Journal of neuroscience : the official journal of the Society for Neuroscience 173 10807937
2011 Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory. Proceedings of the National Academy of Sciences of the United States of America 144 21245308
2014 Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment. Neurobiology of aging 107 25104558
2003 The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted to a distinct synaptic vesicle subpopulation. Molecular biology of the cell 101 14657250
2007 Evidence that the ZNT3 protein controls the total amount of elemental zinc in synaptic vesicles. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 98 17712179
2012 Angiotensin II requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells. PloS one 81 22427991
2005 Vglut1 and ZnT3 co-targeting mechanisms regulate vesicular zinc stores in PC12 cells. Journal of cell science 74 15860731
2009 SLC30A3 responds to glucose- and zinc variations in beta-cells and is critical for insulin production and in vivo glucose-metabolism during beta-cell stress. PloS one 68 19492079
2009 ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain. Molecular neurodegeneration 55 20030848
2000 Deficiencies of hippocampal Zn and ZnT3 accelerate brain aging of Rat. Biochemical and biophysical research communications 48 11118316
2009 SLC30A3 (ZnT3) oligomerization by dityrosine bonds regulates its subcellular localization and metal transport capacity. PloS one 45 19521526
2014 Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis. Journal of neuroscience research 44 25284286
2002 Developmental expression of ZnT3 in mouse brain: correlation between the vesicular zinc transporter protein and chelatable vesicular zinc (CVZ) cells. Glial and neuronal CVZ cells interact. Molecular and cellular neurosciences 36 12401442
2011 ZnT3: a zinc transporter active in several organs. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 35 21866305
2008 ZnT-1, ZnT-3, CaMK II, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats. Toxicology letters 29 19059322
2004 Localization of zinc transporter-3 (ZnT-3) in mouse retina. Vision research 28 15535999
2007 Zinc distribution and expression pattern of ZnT3 in mouse brain. Biological trace element research 27 17916939
2010 siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 26 21208276
2020 Disruption of zinc transporter ZnT3 transcriptional activity and synaptic vesicular zinc in the brain of Huntington's disease transgenic mouse. Cell & bioscience 23 32944220
2016 Common variants in the chromosome 2p23 region containing the SLC30A3 (ZnT3) gene are associated with schizophrenia in female but not male individuals in a large collection of European samples. Psychiatry research 22 27750116
2019 Involvement of the synapse-specific zinc transporter ZnT3 in cadmium-induced hippocampal neurotoxicity. Journal of cellular physiology 21 30714133
2021 Epigenetic targeting of SLC30A3 by HDAC1 is related to the malignant phenotype of glioblastoma. IUBMB life 19 33715270
2016 Zinc transporter 3 (ZnT3) gene deletion reduces spinal cord white matter damage and motor deficits in a murine MOG-induced multiple sclerosis model. Neurobiology of disease 19 27370228
2010 Elevation of zinc transporter ZnT3 protein in the cerebellar cortex of the AbetaPP/PS1 transgenic mouse. Journal of Alzheimer's disease : JAD 19 20164588
2020 Increased Cerebrospinal Fluid Concentration of ZnT3 Is Associated with Cognitive Impairment in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 17 32925049
2019 Effects of social defeat stress and fluoxetine treatment on neurogenesis and behavior in mice that lack zinc transporter 3 (ZnT3) and vesicular zinc. Hippocampus 15 31821659
2017 ZnT3 Gene Deletion Reduces Colchicine-Induced Dentate Granule Cell Degeneration. International journal of molecular sciences 15 29048371
2016 The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 15 26867900
2016 Protective roles of SLC30A3 against endoplasmic reticulum stress via ERK1/2 activation. Biochemical and biophysical research communications 14 27678294
2014 SLC30A3 and SEP15 gene polymorphisms influence the serum concentrations of zinc and selenium in mature adults. Nutrition research (New York, N.Y.) 14 25249019
2017 Leptin treatment prevents long-term abnormalities in cognition, seizure threshold, hippocampal mossy fiber sprouting and ZnT3/CB-D28k expression in a rat developmental "twist" seizure model. Epilepsy research 13 29287786
2016 Zinc Transporter 3 (Znt3) as an Active Substance in the Enteric Nervous System of the Porcine Esophagus. Journal of molecular neuroscience : MN 13 27796869
2017 Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or neuromodulators in the enteric nervous system of the porcine esophagus. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 12 28417221
2013 The effects of interactions between selenium and zinc serum concentration and SEP15 and SLC30A3 gene polymorphisms on memory scores in a population of mature and elderly adults. Genes & nutrition 12 24338343
2020 MicroRNA-5572 Is a Novel MicroRNA-Regulating SLC30A3 in Sporadic Amyotrophic Lateral Sclerosis. International journal of molecular sciences 11 32599739
2012 Neurochemical characterization of zinc transporter 3-like immunoreactive (ZnT3(+)) neurons in the intramural ganglia of the porcine duodenum. Journal of molecular neuroscience : MN 11 22791190
2023 Neuronal Zinc Transporter ZnT3 Modulates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption. Aging and disease 9 37962463
2024 The WFS1-ZnT3-Zn2+ Axis Regulates the Vicious Cycle of Obesity and Depression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39258564
2019 Effects of enriched housing on the neuronal morphology of mice that lack zinc transporter 3 (ZnT3) and vesicular zinc. Behavioural brain research 8 31689442
2005 Adrenalectomy-induced ZnT3 downregulation in mouse hippocampus is followed by vesicular zinc depletion. Neuroscience letters 8 15755519
2024 Cryo-EM structures of the zinc transporters ZnT3 and ZnT4 provide insights into their transport mechanisms. FEBS letters 6 39474773
2020 The Expression of ZnT3 and GFAP Is Potentiated in the Hippocampus of Drug-Resistant Epileptic Rats Induced by Amygdala Kindling. Neuroimmunomodulation 6 33161399
2013 A comparative study on the possible zinc binding sites of the human ZnT3 zinc transporter protein. Dalton transactions (Cambridge, England : 2003) 6 23839275
2022 Variants in the zinc transporter-3 encoding gene (SLC30A3) in schizophrenia and bipolar disorder: Effects on brain glutamate-A pilot study. Frontiers in psychiatry 5 36203844
2019 Elevated zinc transporter ZnT3 in the dentate gyrus of mast cell-deficient mice. The European journal of neuroscience 5 31502721
2024 Genetic deletion of zinc transporter ZnT3 induces progressive cognitive deficits in mice by impairing dendritic spine plasticity and glucose metabolism. Frontiers in molecular neuroscience 4 38807922
2025 Ginsenoside Rb1 combined with Lycium barbarum polysaccharide alleviate the Tripterygium wilfordii polyglycoside-induced oligoasthenozoospermia in mice by inhibiting ZnT3-mediated oxidative stress response. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 3 40233591
2018 Alterations in the Neurobehavioral Phenotype and ZnT3/CB-D28k Expression in the Cerebral Cortex Following Lithium-Pilocarpine-Induced Status Epilepticus: the Ameliorative Effect of Leptin. Biological trace element research 3 29687372
2024 Zinc transporter ZnT3/Slc30a3 has a potential role in zinc ion influx in mouse oocytes. The Journal of reproduction and development 2 39048372
2025 SLC30A3 as a Zinc Transporter-Related Biomarker and Potential Therapeutic Target in Alzheimer's Disease. Genes 1 41300833
2023 A preliminary investigation of the regulatory effect of acupuncture on hippocampal circHDAC2/miR-3065/SLC30A3 axis in CIRI rats. Zhen ci yan jiu = Acupuncture research 1 38146241
2025 ZnT3-TMEM163 Mediates Zinc Homeostasis Imbalance Induced Neurodegeneration in Hippocampus. Frontiers in bioscience (Landmark edition) 0 41504061
2002 [Cloning of ZnT3 cDNA and expression of ZnT3 mRNA in mice]. Wei sheng yan jiu = Journal of hygiene research 0 12561542

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