ArticleProceedings of the National Academy of Sciences of the United States of America2015
Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 109 citations in OpenAlex.
- Scales of Postsynaptic Nanostructure: Molecules, Nanoclusters, and Nanodomains.Advances in neurobiology · 2026Review
- Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche.The Journal of clinical investigation · 2025Article
- Nonionic signaling rapidly remodels postsynaptic DLG to induce retrograde homeostatic plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Non-ionotropic NMDAR signalling activates Panx1 to induce P2X4R-dependent long-term depression in the hippocampus.The Journal of physiology · 2025Article
- Article
- Non-ionotropic signaling through the NMDA receptor GluN2B carboxy-terminal domain drives dendritic spine plasticity and reverses fragile X phenotypes.Cell reports · 2025Article
- Structure-Activity Relationship of NMDA Receptor Ligands and Their Activities on the ERK Activation through Metabotropic Signaling Pathway.Biomolecules & therapeutics · 2025Article
- N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.Molecular neurobiology · 2025Article
- Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices.Frontiers in neuroanatomy · 2025Article
- Metabotropic NMDAR Signaling Contributes to Sex Differences in Synaptic Plasticity and Episodic Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Article
- d-Serine Inhibits Non-ionotropic NMDA Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
- Metabotropic NMDA Receptor Signaling Contributes to Sex Differences in Synaptic Plasticity and Episodic Memory.bioRxiv : the preprint server for biology · 2024Article
- Fluorescence lifetime imaging of AMPA receptor endocytosis in living neurons: effects of Aβ and PP1.Frontiers in molecular neuroscience · 2024Article
- Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment.Cell reports · 2023Article
- Nociceptor activity induces nonionotropic NMDA receptor signaling to enable spinal reconsolidation and reverse pathological pain.Science advances · 2023Article
- NMDA Receptor and Its Emerging Role in Cancer.International journal of molecular sciences · 2023Review
- Reduced d-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia.Neurobiology of disease · 2022Article
- Ion flux-independent NMDA receptor signaling.Neuropharmacology · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The NMDA receptor (R) plays important roles in brain physiology and pathology as an ion channel. Here we examine the ion flow-independent coupling of agonist to the NMDAR cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic domains of GluN1 subunits of NMDARs expressed in neurons. Different neuronal compartments display varying levels of FRET, consistent with different NMDARcd conformations. Agonist binding drives a rapid and transient ion flow-independent reduction in FRET between GluN1 subunits within individual NMDARs. Intracellular infusion of an antibody targeting the GluN1 cytoplasmic domain blocks agonist-driven FRET changes in the absence of ion flow, supporting agonist-driven movement of the NMDARcd. These studies indicate that extracellular ligand binding to the NMDAR can transmit conformational information into the cell in the absence of ion flow.
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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.