ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Molecular mechanisms contributing to TARP regulation of channel conductance and polyamine block of calcium-permeable AMPA receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- 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
- Intracellular Spermine Is a Key Player in GSG1L's Regulation of Calcium-Permeable AMPAR Channel Conductance and Recovery from Desensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The open gate of the AMPA receptor forms a CaNature structural & molecular biology · 2024Article
- Enhanced functional detection of synaptic calcium-permeable AMPA receptors using intracellular NASPM.eLife · 2023Article
- Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome.American journal of human genetics · 2022Article
- Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor.Nature communications · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3.PLoS genetics · 2021Article
- CaThe Journal of physiology · 2021Article
- Nonselective cation permeation in an AMPA-type glutamate receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Auxiliary Subunits Control Function and Subcellular Distribution of AMPA Receptor Complexes in NG2 Glia of the Developing Hippocampus.Frontiers in cellular neuroscience · 2021Article
- Interplay between Gating and Block of Ligand-Gated Ion Channels.Brain sciences · 2020Review
- Article
- Homomeric GluA2(R) AMPA receptors can conduct when desensitized.Nature communications · 2019Article
- Stargazin and γ4 slow the channel opening and closing rates of GluA4 AMPA receptors.Scientific reports · 2019Article
- Polyamine-mediated channel block of ionotropic glutamate receptors and its regulation by auxiliary proteins.The Journal of biological chemistry · 2018Review
- Ion permeation in ionotropic glutamate receptors: Still dynamic after all these years.Current opinion in physiology · 2018Article
- Uncorking AMPA receptors.The Journal of general physiology · 2018Article
- Stargazin and cornichon-3 relieve polyamine block of AMPA receptors by enhancing blocker permeation.The Journal of general physiology · 2018Article
- The Role of Polyamine-Dependent Facilitation of Calcium Permeable AMPARs in Short-Term Synaptic Enhancement.Frontiers in cellular neuroscience · 2018Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Many properties of fast synaptic transmission in the brain are influenced by transmembrane AMPAR regulatory proteins (TARPs) that modulate the pharmacology and gating of AMPA-type glutamate receptors (AMPARs). Although much is known about TARP influence on AMPAR pharmacology and kinetics through their modulation of the extracellular ligand-binding domain (LBD), less is known about their regulation of the ion channel region. TARP-induced modifications in AMPAR channel behavior include increased single-channel conductance and weakened block of calcium-permeable AMPARs (CP-AMPARs) by endogenous intracellular polyamines. To investigate how TARPs modify ion flux and channel block, we examined the action of γ-2 (stargazin) on GluA1 and GluA4 CP-AMPARs. First, we compared the permeation of organic cations of different sizes. We found that γ-2 increased the permeability of several cations but not the estimated AMPAR pore size, suggesting that TARP-induced relief of polyamine block does not reflect altered pore diameter. Second, to determine whether residues in the TARP intracellular C-tail regulate polyamine block and channel conductance, we examined various γ-2 C-tail mutants. We identified the membrane proximal region of the C terminus as crucial for full TARP-attenuation of polyamine block, whereas complete deletion of the C-tail markedly enhanced the TARP-induced increase in channel conductance; thus, the TARP C-tail influences ion permeation. Third, we identified a site in the pore-lining region of the AMPAR, close to its Q/R site, that is crucial in determining the TARP-induced changes in single-channel conductance. This conserved residue represents a site of TARP action, independent of the AMPAR LBD.
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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.