ArticleNature structural & molecular biology2023
Modulation of GluA2-γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 27 citations in OpenAlex.
- Tunable AMPA receptor function via recurrent evolution of heterotetramers.The Journal of general physiology · 2026Article
- Pre-activation and gating pathway of AMPA receptors revealed by full and partial agonists.Nature structural & molecular biology · 2026Article
- Tuning of AMPA receptor activation by inhibitory auxiliary subunits and epilepsy-associated disease mutations.Nature communications · 2026Article
- The AMPA receptor life cycle: assembly, regulation and synaptic diversity.Nature reviews. Neuroscience · 2026Review
- Assembly and gating mechanism of native AMPA receptors from the cerebellum.Cell research · 2026Article
- Open-channel block of human TRPV6 by polyamine spermine.Nature communications · 2026Article
- Auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric GluA1/A2 AMPA receptor core.Nature communications · 2026Article
- Trafficking of the human NaProtein science : a publication of the Protein Society · 2026Article
- Structural basis for activation and conformational plasticity of the GluA4 AMPA receptor.Nature communications · 2026Article
- Efficient and rapid isolation of native AMPA receptor complexes for cryo-EM.Protein science : a publication of the Protein Society · 2026Article
- Structural insights into kainate receptor desensitization.Nature communications · 2025Article
- GluA4 AMPA receptor gating mechanisms and modulation by auxiliary proteins.Nature structural & molecular biology · 2025Article
- Early-life gut microbiome maturity regulates blood-brain barrier and cognitive development.Gut microbes · 2025Article
- Activation of kainate receptor GluK2-Neto2 complex.Nature structural & molecular biology · 2025Article
- Atomistic mechanisms of calcium permeation modulated by Q/R editing and selectivity filter mutations in GluA2 AMPA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Article
- Structure of transmembrane AMPA receptor regulatory protein subunit γ2.Nature communications · 2025Article
- Endothelium glutamate receptors in brain pathology.Frontiers in pharmacology · 2025Review
- Structure and gating of kainate receptors.Frontiers in pharmacology · 2025Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron microscopy structures of rat GluA2 AMPAR complexes with inhibitory mouse γ5 and potentiating human cornichon-2 (CNIH2) auxiliary subunits. CNIH2 appears to destabilize the desensitized state of the complex by reducing the separation of the upper lobes in ligand-binding domain dimers. At the same time, CNIH2 stabilizes binding of polyamine spermidine to the selectivity filter of the closed ion channel. Nevertheless, CNIH2, and to a lesser extent γ5, attenuate polyamine block of the open channel and reduce the potency of the antiepileptic drug perampanel that inhibits the synaptic complex allosterically by binding to sites in the ion channel extracellular collar. These findings illustrate the fine-tuning of synaptic complex structure and function in an auxiliary subunit-dependent manner, which is critical for the study of brain region-specific neurotransmission and design of therapeutics for disease treatment.
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