ArticleFrontiers in molecular neuroscience2018
Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons.
Article in Frontiers in molecular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- The role of zinc homeostasis in major depressive disorder: heterogeneous pathological mechanisms and therapeutic implications.Annals of medicine · 2026Review
- Disrupted Development of the mPFC-Thalamic Circuit in Shank3Molecular psychiatry · 2026Article
- Hypersynchronous iPSC-derived SHANK2 neuronal networks are rescued by mGluR5 agonism.Stem cell reports · 2025Article
- Shank3 establishes AMPA receptor subunit composition at cerebellar mossy fiber-granule cell synapses and is associated with altered regional microglial morphology.Neurobiology of disease · 2025Article
- Metallothionein III Mediates CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Deciphering the Role of Shank3 in Dendritic Morphology and Synaptic Function Across Postnatal Developmental Stages in the Shank3B KO Mouse.Neuroscience bulletin · 2025Article
- Establishing a Mouse Model of NL3R617W-Associated Autism Spectrum Disorder for a Functional Study.Actas espanolas de psiquiatria · 2025Article
- MSC-exosomes pretreated by Danshensu extracts pretreating to target the hsa-miR-27a-5p and STAT3-SHANK2 to enhanced antifibrotic therapy.Stem cell research & therapy · 2025Article
- Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism.Scientific reports · 2025Article
- 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
- mRNA nuclear retention reduces AMPAR expression and promotes autistic behavior in UBE3A-overexpressing mice.EMBO reports · 2024Article
- Roles of AMPA receptors in social behaviors.Frontiers in synaptic neuroscience · 2024Review
- Neurodevelopmental Consequences of Dietary Zinc Deficiency: A Status Report.Biological trace element research · 2023Review
- GluA1-Shank3 interaction decreases in response to chronic neuronal depolarization.Neuroscience letters · 2023Article
- ΔInternational journal of molecular sciences · 2023Article
- Methylmalonic Acid Impairs Cell Respiration and Glutamate Uptake in C6 Rat Glioma Cells: Implications for Methylmalonic Acidemia.Cellular and molecular neurobiology · 2023Article
- The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neuronsFrontiers in cellular neuroscience · 2023Article
- The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Elemental Dynamics in Hair Accurately Predict Future Autism Spectrum Disorder Diagnosis: An International Multi-Center Study.Journal of clinical medicine · 2022Article
- Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A.Neuroscience letters · 2022Article
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
During development, pyramidal neurons undergo dynamic regulation of AMPA receptor (AMPAR) subunit composition and density to help drive synaptic plasticity and maturation. These normal developmental changes in AMPARs are particularly vulnerable to risk factors for Autism Spectrum Disorders (ASDs), which include loss or mutations of synaptic proteins and environmental insults, such as dietary zinc deficiency. Here, we show how Shank2 and Shank3 mediate a zinc-dependent regulation of AMPAR function and subunit switch from GluA2-lacking to GluA2-containing AMPARs. Over development, we found a concomitant increase in Shank2 and Shank3 with GluA2 at synapses, implicating these molecules as potential players in AMPAR maturation. Since Shank activation and function require zinc, we next studied whether neuronal activity regulated postsynaptic zinc at glutamatergic synapses. Zinc was found to increase transiently and reversibly with neuronal depolarization at synapses, which could affect Shank and AMPAR localization and activity. Elevated zinc induced multiple functional changes in AMPAR, indicative of a subunit switch. Specifically, zinc lengthened the decay time of AMPAR-mediated synaptic currents and reduced their inward rectification in young hippocampal neurons. Mechanistically, both Shank2 and Shank3 were necessary for the zinc-sensitive enhancement of AMPAR-mediated synaptic transmission and act in concert to promote removal of GluA1 while enhancing recruitment of GluA2 at pre-existing Shank puncta. These findings highlight a cooperative local dynamic regulation of AMPAR subunit switch controlled by zinc signaling through Shank2 and Shank3 to shape the biophysical properties of developing glutamatergic synapses. Given the zinc sensitivity of young neurons and its dependence on Shank2 and Shank3, genetic mutations and/or environmental insults during early development could impair synaptic maturation and circuit formation that underlie ASD etiology.
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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.