ArticleThe Journal of physiology2012
GluN1 splice variant control of GluN1/GluN2D NMDA receptors.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 65 citations in OpenAlex.
- SIK3 controls synaptic localization of NMDA receptors by phosphorylating GluN1.Nature neuroscience · 2026Article
- GluN2D NMDA Receptors: Bridging Physiology and Pathology.Biological psychiatry · 2026Review
- Bidirectional control of vesicular GABA release, LTP, and amotivation by GluN2D-selective allosteric modulators and ketamine.Cell reports · 2026Article
- Selective enhancement of the interneuron network and gamma-band power via GluN2C/GluN2D NMDA receptor potentiation.The Journal of physiology · 2025Article
- Membrane Association of Intrinsically Disordered Proteins.Annual review of biophysics · 2025Review
- Regulation of NMDAR activation efficiency by environmental factors and subunit composition.The Journal of general physiology · 2025Article
- Research Progress on NMDA Receptor Enhancement Drugs for the Treatment of Depressive Disorder.CNS drugs · 2024Review
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Selective Cell-Surface Expression of Triheteromeric NMDA Receptors.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Downstream Allosteric Modulation of NMDA Receptors by 3-Benzazepine Derivatives.Molecular neurobiology · 2023Article
- Structural insights into NMDA receptor pharmacology.Biochemical Society transactions · 2023Review
- Pharmacological Potential of 3-Benzazepines in NMDAR-Linked Pathophysiological Processes.Biomedicines · 2023Review
- Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits.Nature structural & molecular biology · 2023Article
- GluN2A-Selective NMDA Receptor Antagonists: Mimicking the U-Shaped Bioactive Conformation of TCN-201 by a [2.2]Paracyclophane System.ChemMedChem · 2022Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Alternative splicing of GluN1 gates glycine site-dependent nonionotropic signaling by NMDAR receptors.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data.Cellular and molecular life sciences : CMLS · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
NMDA receptors are ionotropic glutamate receptors that mediate a slow, Ca2+-permeable component of excitatory synaptic transmission in the central nervous system. Recombinant GluN1-1a/GluN2D receptors are characterized by low channel open probability and prolonged deactivation time course following the removal of agonist. Here, we show that the deactivation time course, agonist potency, and single channel properties of GluN2D-containing NMDA receptors are modulated by alternative RNA splicing of GluN1. Our results demonstrate that GluN1 exon 5, which encodes a 21-amino-acid insert in the amino-terminal domain, is a key determinant of GluN1/GluN2D receptor function. GluN1-1b/GluN2D receptors, which contain the residues encoded by exon 5, deactivate with a dual exponential time course described by a τFAST of 410 ms and a τSLOW of 1100 ms. This time course is 3-fold more rapid than that for exon 5-lacking GluN1-1a/GluN2D, which deactivates with a τFAST of 1100 ms and a τSLOW of 3400 ms. Exon 5-containing NMDA receptors also have a two-fold higher open probability (0.037) than exon 5-lacking receptors (0.017). Furthermore, inclusion of exon 5-encoded residues within the GluN1-1b subunit decreases the potency for the endogenous agonist l-glutamate. Evaluation of receptor kinetics for NMDA receptors containing mutated GluN1-1b subunits and wild-type GluN2D identified residue Lys211 in GluN1-1b as a key determinant of exon 5 control of the deactivation time course and glutamate potency. Evaluation of a kinetic model of GluN1/GluN2D gating suggests that residues encoded by exon 5 influence several rate-limiting steps. These data demonstrate that the GluN1 subunit is a key determinant of the kinetic and pharmacological properties of GluN2D-containing NMDA receptors.
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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.