ArticleNeuroscience letters2022
Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A.
Article in Neuroscience letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.Biological trace element research · 2026Review
- Review
- Prenatal exposure to particulate matter impairs offspring behavior via hippocampal NMDA receptor reduction: an in vivo and ex vivo study.Environment international · 2026Article
- ZIP-ZnT1 complexes mediate a local ZnCellular and molecular life sciences : CMLS · 2026Article
- The serum trace metal signature distinguishes patients with psychiatric disorders from healthy controls.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Pharmacotherapeutic strategies for the treatment of anorexia nervosa - novel targets to break a vicious cycle.Expert opinion on pharmacotherapy · 2024Review
- Structural insights into human zinc transporter ZnT1 mediated ZnEMBO reports · 2024Article
- Trans-synaptic Association of Vesicular Zinc Transporter 3 and Shank3 Supports Synapse-Specific Dendritic Spine Structure and Function in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study.Actas espanolas de psiquiatria · 2024Article
- The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.Neurochemistry international · 2024Article
- Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies.Current medicinal chemistry · 2024Review
- Association between serum copper, zinc, and selenium concentrations and depressive symptoms in the US adult population, NHANES (2011-2016).BMC psychiatry · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Zinc, loaded into glutamate-containing presynaptic vesicles and released into the synapse in an activity-dependent manner, modulates neurotransmission through its actions on postsynaptic targets, prominently via high-affinity inhibition of GluN2A-containing NMDA receptors. Recently, we identified a postsynaptic transport mechanism that regulates endogenous zinc inhibition of NMDARs. In this new model of zinc regulation, the postsynaptic transporter ZnT1 mediates zinc inhibition of NMDARs by binding to GluN2A. Through this interaction, ZnT1, a transporter that moves zinc from the cytoplasm to the extracellular domain, generates a zinc microdomain that modulates NMDAR-mediated neurotransmission. As ZnT1 expression is transcriptionally driven by the metal-responsive transcription factor 1 (MTF-1), we found that intracellular zinc strongly drives MTF-1 in cortical neurons in vitro and increases the number of GluN2A-ZnT1 interactions, thereby enhancing tonic zinc inhibition of NMDAR-mediated currents. Importantly, this effect is absent when the interaction between GluN2A and ZnT1 is disrupted by a cell-permeable peptide. These results suggest that zinc-regulated gene expression can dynamically regulate NMDAR-mediated synaptic processes.
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Registered trials
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