ArticleFrontiers in cellular neuroscience2014
DYRK1A-mediated phosphorylation of GluN2A at Ser(1048) regulates the surface expression and channel activity of GluN1/GluN2A receptors.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Increased NMDAR activity and GluN2A-NMDAR silent synapse expansion induced by chronic benzodiazepine treatment.Neuropharmacology · 2025Article
- Regulation of Synaptic NMDA Receptor Activity by Post-Translational Modifications.Neurochemical research · 2025Review
- DYRK1A roles in human neural progenitors.Frontiers in neuroscience · 2025Article
- DYRK1A in the physiology and pathology of the neuron-astrocyte axis.Frontiers in neuroscience · 2025Review
- TargetingInternational journal of molecular sciences · 2024Review
- Dissecting the contribution of human chromosome 21 syntenic regions to recognition memory processes in adult and aged mouse models of Down syndrome.Frontiers in behavioral neuroscience · 2024Article
- Insights from the protein interaction Universe of the multifunctional "Goldilocks" kinase DYRK1A.Frontiers in cell and developmental biology · 2023Review
- Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome.Scientific reports · 2022Article
- The Omnipresence of DYRK1A in Human Diseases.International journal of molecular sciences · 2022Review
- Review
- Building a Bridge Between NMDAR-Mediated Excitotoxicity and Mitochondrial Dysfunction in Chronic and Acute Diseases.Cellular and molecular neurobiology · 2021Review
- Regulation of the NMDA receptor by its cytoplasmic domains: (How) is the tail wagging the dog?Neuropharmacology · 2021Review
- Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome.PLoS genetics · 2021Article
- GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways.International journal of molecular sciences · 2021Review
- Intellectual disability: dendritic anomalies and emerging genetic perspectives.Acta neuropathologica · 2021Review
- Ethanol-Induced Changes in Brain of Transgenic Mice Overexpressing DYRK1A.Molecular neurobiology · 2020Article
- [Molecules (Basel, Switzerland) · 2019Article
- Vascular defects ofDisease models & mechanisms · 2019Article
- The Developmental Shift of NMDA Receptor Composition Proceeds Independently of GluN2 Subunit-Specific GluN2 C-Terminal Sequences.Cell reports · 2018Article
- Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A.Disease models & mechanisms · 2018Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N-methyl-D-aspartate glutamate receptors (NMDARs) play a pivotal role in neural development and synaptic plasticity, as well as in neurological disease. Since NMDARs exert their function at the cell surface, their density in the plasma membrane is finely tuned by a plethora of molecules that regulate their production, trafficking, docking and internalization in response to external stimuli. In addition to transcriptional regulation, the density of NMDARs is also influenced by post-translational mechanisms like phosphorylation, a modification that also affects their biophysical properties. We previously described the increased surface expression of GluN1/GluN2A receptors in transgenic mice overexpressing the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), suggesting that DYRK1A regulates NMDARs. Here we have further investigated whether the density and activity of NMDARs were modulated by DYRK1A phosphorylation. Accordingly, we show that endogenous DYRK1A is recruited to GluN2A-containing NMDARs in the adult mouse brain, and we identify a DYRK1A phosphorylation site at Ser(1048) of GluN2A, within its intracellular C-terminal domain. Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser(1048) hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons. Furthermore, GluN2A phosphorylation at Ser(1048) increases the current density and potentiates the gating of GluN1/GluN2A receptors. We conclude that DYRK1A is a direct regulator of NMDA receptors and we propose a novel mechanism for the control of NMDAR activity in neurons.
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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.