ArticleScientific reports2016
P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
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- ATP Release Deficiency through Astrocytic Connexin 43 in the Dorsal Hippocampus Promotes Depressive- and Anxiety-Like Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Synaptic pruning following NMDAR-dependent LTD preferentially affects isolated synapses.iScience · 2025Article
- Non-ionotropic NMDAR signalling activates Panx1 to induce P2X4R-dependent long-term depression in the hippocampus.The Journal of physiology · 2025Article
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- Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.Purinergic signalling · 2025Review
- Synapse-specific structural plasticity that protects and refines local circuits during LTP and LTD.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Progress on functions of intracellular domainZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Role for Astrocytes in mGluR-Dependent LTD in the Neocortex and Hippocampus.Brain sciences · 2022Article
- Increased surface P2X4 receptors by mutant SOD1 proteins contribute to ALS pathogenesis in SOD1-G93A mice.Cellular and molecular life sciences : CMLS · 2022Article
- Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms.The FEBS journal · 2022Review
- P2X7 Receptors and TMEM16 Channels Are Functionally Coupled with Implications for Macropore Formation and Current Facilitation.International journal of molecular sciences · 2021Article
- NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95.Nature communications · 2021Article
- Regulation of membrane NMDA receptors by dynamics and protein interactions.The Journal of cell biology · 2021Review
- MeCP2 gates spatial learning-induced alternative splicing events in the mouse hippocampus.Molecular brain · 2020Article
- Implication of Neuronal Versus Microglial P2X4 Receptors in Central Nervous System Disorders.Neuroscience bulletin · 2020Review
- Cross-Talk between P2X and NMDA Receptors.International journal of molecular sciences · 2020Article
- Inorganic Polyphosphate Regulates AMPA and NMDA Receptors and Protects Against Glutamate Excitotoxicity via Activation of P2Y Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Salicylate-Induced Ototoxicity of Spiral Ganglion Neurons: CaNeurotoxicity research · 2019Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasticity at excitatory synapses can be induced either by synaptic release of glutamate or the release of gliotransmitters such as ATP. Recently, we showed that postsynaptic P2X2 receptors activated by ATP released from astrocytes downregulate synaptic AMPAR, providing a novel mechanism by which glial cells modulate synaptic activity. ATP- and lNMDA-induced depression in the CA1 region of the hippocampus are additive, suggesting distinct molecular pathways. AMPARs are homo-or hetero-tetramers composed of GluA1-A4. Here, we first show that P2X2-mediated AMPAR inhibition is dependent on the subunit composition of AMPAR. GluA3 homomers are insensitive and their presence in heteromers alters P2X-mediated inhibition. Using a mutational approach, we demonstrate that the two CaMKII phosphorylation sites S567 and S831 located in the cytoplasmic Loop1 and C-terminal tail of GluA1 subunits, respectively, are critical for P2X2-mediated AMPAR inhibition recorded from co-expressing Xenopus oocytes and removal of surface AMPAR at synapses of hippocampal neurons imaged by the super-resolution dSTORM technique. Finally, using phosphorylation site-specific antibodies, we show that P2X-induced depression in hippocampal slices produces a dephosphorylation of the GluA1 subunit at S567, contrary to NMDAR-mediated LTD. These findings indicate that GluA1 phosphorylation of S567 and S831 is critical for P2X2-mediated AMPAR internalization and ATP-driven synaptic depression.
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