ArticleProceedings of the National Academy of Sciences of the United States of America2020
Tyrosine phosphorylation of the AMPA receptor subunit GluA2 gates homeostatic synaptic plasticity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- TNF-dependent regulation of synaptic plasticity and neuronal activity: implications for psychiatric disorders.Molecular psychiatry · 2026Review
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Nature communications · 2026Article
- Posttranslational modifications of AMPA receptors in synaptic function and memory.Cellular and molecular life sciences : CMLS · 2026Review
- Dysregulated GluA2-Y876 phosphorylation contributes to loss of synaptic upscaling in GRIP1 mutant mice with reduced sociability and increased repetitive behavior.Molecular psychiatry · 2026Article
- Convergence and divergence of molecular mechanisms in Hebbian and homeostatic plasticity.Frontiers in synaptic neuroscience · 2026Review
- Harnessing metabolic control for synaptic stability: REST/NRSF links glycolytic inhibition to excitatory neurotransmission.The Journal of physiology · 2025Article
- ADAR2-mediated Q/R editing of GluA2 in homeostatic synaptic plasticity.Science signaling · 2025Article
- AMPA Receptors in Synaptic Plasticity, Memory Function, and Brain Diseases.Cellular and molecular neurobiology · 2025Review
- Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy.Translational psychiatry · 2025Article
- Neuroplasticity in autism spectrum disorder: a systematic review.Dementia & neuropsychologia · 2025Review
- LncRNA MSTRG.13,871/miR155-5p/Grip1 network involved in the post-cardiac arrest brain injury.Scientific reports · 2024Article
- Neuroplasticity in the transition from acute to chronic pain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.Scientific reports · 2023Article
- A bidirectional switch in the Shank3 phosphorylation state biases synapses toward up- or downscaling.eLife · 2022Article
- Membrane lipid rafts are required for AMPA receptor tyrosine phosphorylation.Frontiers in synaptic neuroscience · 2022Article
- Sensorimotor Perturbation Induces Late and Transient Molecular Synaptic Proteins Activation and Expression Changes.Journal of molecular neuroscience : MN · 2021Article
- Dynamic bi-directional phosphorylation events associated with the reciprocal regulation of synapses during homeostatic up- and down-scaling.Cell reports · 2021Article
- Astrocytes in Neural Circuits: Key Factors in Synaptic Regulation and Potential Targets for Neurodevelopmental Disorders.Frontiers in molecular neuroscience · 2021Review
- Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.Current neuropharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hebbian plasticity, comprised of long-term potentiation (LTP) and depression (LTD), allows neurons to encode and respond to specific stimuli; while homeostatic synaptic scaling is a counterbalancing mechanism that enables the maintenance of stable neural circuits. Both types of synaptic plasticity involve the control of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) abundance, which is modulated by AMPAR phosphorylation. To address the necessity of GluA2 phospho-Y876 in synaptic plasticity, we generated phospho-deficient GluA2 Y876F knock-in mice. We show that, while GluA2 phospho-Y876 is not necessary for Hebbian plasticity, it is essential for both in vivo and in vitro homeostatic upscaling. Bidirectional changes in GluA2 phospho-Y876 were observed during homeostatic scaling, with a decrease during downscaling and an increase during upscaling. GluA2 phospho-Y876 is necessary for synaptic accumulation of glutamate receptor interacting protein 1 (GRIP1), a crucial scaffold protein that delivers AMPARs to synapses, during upscaling. Furthermore, increased phosphorylation at GluA2 Y876 increases GluA2 binding to GRIP1. These results demonstrate that AMPAR trafficking during homeostatic upscaling can be gated by a single phosphorylation site on the GluA2 subunit.
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