ArticleScience advances2020
Synaptic zinc inhibition of NMDA receptors depends on the association of GluN2A with the zinc transporter ZnT1.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- Zinc homeostasis imbalance: Potential therapeutic value in neurodegenerative diseases.Neural regeneration research · 2026Article
- State-specific inhibition of NMDA receptors by memantine provides insight into NMDAR channel blocker tolerability.Science advances · 2026Article
- An Ultraresponsive Green Biosensor for Robust in Vivo Imaging of Synaptic Zinc Dynamics.ACS sensors · 2026Article
- ZIP-ZnT1 complexes mediate a local ZnCellular and molecular life sciences : CMLS · 2026Article
- Metallothionein III Mediates CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- hpGRISZ: a high-performance fluorescent biosensor for in vivo imaging of synaptic zinc dynamics.bioRxiv : the preprint server for biology · 2025Article
- Prospects and challenges in NMDAR signaling in spinal cord injury recovery and neural circuit remodeling.Regenerative therapy · 2025Review
- Zinc-Dependent Modulation of Dopamine Release and Uptake Is Altered in Parkinson's Disease Model Zebrafish.ACS chemical neuroscience · 2025Article
- The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- SENP6-Mediated deSUMOylation of Nrf2 Exacerbates Neuronal Oxidative Stress Following Cerebral Ischemia and Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides.Molecules (Basel, Switzerland) · 2025Article
- Structural insights into human zinc transporter ZnT1 mediated ZnEMBO reports · 2024Article
- Cell-type-specific enhancement of deviance detection by synaptic zinc in the mouse auditory cortex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- On the genesis and unique functions of zinc neuromodulation.Journal of neurophysiology · 2024Review
- The physiological and pathophysiological roles of copper in the nervous system.The European journal of neuroscience · 2024Review
- Cortical Zinc Signaling Is Necessary for Changes in Mouse Pupil Diameter That Are Evoked by Background Sounds with Different Contrasts.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.Neurochemistry international · 2024Article
- Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The NMDA receptor (NMDAR) is inhibited by synaptically released zinc. This inhibition is thought to be the result of zinc diffusion across the synaptic cleft and subsequent binding to the extracellular domain of the NMDAR. However, this model fails to incorporate the observed association of the highly zinc-sensitive NMDAR subunit GluN2A with the postsynaptic zinc transporter ZnT1, which moves intracellular zinc to the extracellular space. Here, we report that disruption of ZnT1-GluN2A association by a cell-permeant peptide strongly reduced NMDAR inhibition by synaptic zinc in mouse dorsal cochlear nucleus synapses. Moreover, synaptic zinc inhibition of NMDARs required postsynaptic intracellular zinc, suggesting that cytoplasmic zinc is transported by ZnT1 to the extracellular space in close proximity to the NMDAR. These results challenge a decades-old dogma on how zinc inhibits synaptic NMDARs and demonstrate that presynaptic release and a postsynaptic transporter organize zinc into distinct microdomains to modulate NMDAR neurotransmission.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.