ArticleMolecular pharmacology2016
Pharmacology and Structural Analysis of Ligand Binding to the Orthosteric Site of Glutamate-Like GluD2 Receptors.
Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- GluD1 is localized at cholinergic synapses and is an acetylcholine receptor.Molecular psychiatry · 2026Article
- Calcitonin Gene-Related Peptide (CGRP)-Containing Terminals in the Central Amygdala of Mice and Monkeys: Ultrastructural Analysis and Subsynaptic Expression of GluD1.The European journal of neuroscience · 2026Article
- GluD1 at the synaptic crossroads: from domain structure to circuit dysfunction.Acta pharmacologica Sinica · 2026Review
- Glutamate Delta 1 Receptor in Synapses, Circuits, and Disease.The European journal of neuroscience · 2026Review
- Lack of evidence for direct ligand-gated ion channel activity of GluD receptors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses.Molecular psychiatry · 2024Article
- Loss of activation by GABA in vertebrate delta ionotropic glutamate receptors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants.Human molecular genetics · 2024Article
- GluD receptors are functional ion channels.Biophysical journal · 2023Review
- Homecoming of the estranged GluD channels.Trends in neurosciences · 2022Article
- Delta glutamate receptors are functional glycine- and ᴅ-serine-gated cation channels in situ.Science advances · 2021Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- An emerging map of glutamate delta 1 receptors in the forebrain.Neuropharmacology · 2021Review
- Structural biology and thermodynamics of GluD receptors.Neuropharmacology · 2021Review
- Article
- D-Serine Potently Drives Ligand-Binding Domain Closure in the Ionotropic Glutamate Receptor GluD2.Structure (London, England : 1993) · 2020Article
- Ethylene-independent signaling by the ethylene precursor ACC in Arabidopsis ovular pollen tube attraction.Nature communications · 2020Article
- Striatal glutamate delta-1 receptor regulates behavioral flexibility and thalamostriatal connectivity.Neurobiology of disease · 2020Article
- Cryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture.Nature structural & molecular biology · 2020Article
- Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The GluD2 receptor is a fundamental component of postsynaptic sites in Purkinje neurons, and is required for normal cerebellar function. GluD2 and the closely related GluD1 are classified as members of the ionotropic glutamate receptor (iGluR) superfamily on the basis of sequence similarity, but do not bind l-glutamate. The amino acid neurotransmitter D-Ser is a GluD2 receptor ligand, and endogenous D-Ser signaling through GluD2 has recently been shown to regulate endocytosis of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type iGluRs during synaptic plasticity in the cerebellum, such as long-term depression. Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activity of analogs of D-Ser and GluN1 glycine site competitive antagonists at GluD2 receptors containing the lurcher mutation (GluD2(LC)), which promotes spontaneous channel activation. We identify several compounds that modulate GluD2(LC), including a halogenated alanine analog as well as the kynurenic acid analog 7-chloro-4-oxo-1H-quinoline-2-carboxylic acid (7-chlorokynurenic acid; 7-CKA). By correlating thermodynamic and structural data for 7-CKA binding to the isolated GluD2 ligand binding domain (GluD2-LBD), we find that binding 7-CKA to GluD2-LBD differs from D-Ser by inducing an intermediate cleft closure of the clamshell-shaped LBD. The GluD2 ligands identified here can potentially serve as a starting point for development of GluD2-selective ligands useful as tools in studies of the signaling role of the GluD2 receptor in the brain.
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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.