The δ2 glutamate receptor gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites
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Significance: Long-term depression (LTD) commonly affects learning and memory in various brain regions. Although LTD in the cerebellum absolutely requires δ2 glutamate receptors, its underlying mechanisms remain elusive. LTD is caused by endocytosis of AMPA receptors, which is triggered by activity-induced serine phosphorylation of the GluA2 subunit. Our work showed that this serine phosphorylation required prior dephosphorylation of the nearby tyrosine residue. By interaction with a tyrosine phosphatase, δ2 glutamate receptors regulated tyrosine dephosphorylation status of GluA2 to gate inducibility of LTD. These findings will provide better understanding of general mechanisms regulating AMPA receptor endocytosis during synaptic plasticity.
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Dephosphorylation of GluA2 Y876 by tyrosine phosphatase PTPMEG is necessary for S880 phosphorylation and expression of cerebellar LTD.
“Dephosphorylation of GluA2 Y876 by tyrosine phosphatase PTPMEG was necessary for S880 phosphorylation and expression of cerebellar LTD (Kohda et al., 2013).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Kohda et al., 2013
In cerebellar Purkinje neurons, phosphorylation of GluA2 Y876 inhibits subsequent phosphorylation of GluA2 S880.
“In cerebellar Purkinje neurons, phosphorylation of GluA2 Y876 has been shown to inhibit subsequent phosphorylation of GluA2 S880 (Figure 1) (Kohda et al., 2013).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Kohda et al., 2013
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Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue
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Advances in the Pathogenesis of Auto-antibody-Induced Cerebellar Synaptopathies
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The role of Cbln1 on Purkinje cell synapse formation
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Self-citationGluD receptors are functional ion channels
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Unlocking the secrets of the δ2 glutamate receptor
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Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher Mice
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Self-citationCerebellar long-term depression and auto-immune target of auto-antibodies: the concept of LTDpathies
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LTDpathies: a Novel Clinical Concept
Mitoma, H., Honnorat, J., Yamaguchi, K., & Manto, M. U. (2021) · The Cerebellum · doi:10.1007/s12311-021-01259-2 · Cited by 8 · see citing works
SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD
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PTPN4 germline variants result in aberrant neurodevelopment and growth
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Structural biology and thermodynamics of GluD receptors
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GluD1 at the synaptic crossroads: from domain structure to circuit dysfunction
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Automatic Bayesian Weighting for SAXS Data
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Involvement of GluD2 in Fear-Conditioned Bradycardia in Mice
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Self-citationLong-Term Depression at Parallel Fiber-Purkinje Cell Synapses
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Self-citationDelta Glutamate Receptor (GluD1, GluD2)
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Physiological Functions of d-Serine Mediated Through δ2 Glutamate Receptors in the Cerebellum
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Delta Glutamate Receptor (GluD1, GluD2)
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Long Term Depression in the Granule Cell-Purkinje Cell Synapse
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Long-Term Depression at Parallel Fiber–Purkinje Cell Synapses
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Etude structurale et fonctionnelle de la phosphatase humaine PTPN4
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Transport intracellulaire des récepteurs AMPA et régulation par leurs protéines associées
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- Authors
- Kohda, K., Kakegawa, W., Matsuda, S., Yamamoto, T., Hirano, H., & Yuzaki, M.
- Affiliations
- Keio University (JP)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Yokohama City University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-02-19
- Volume
- 110
- Issue
- 10
- Pages
- E948-57
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3593918
- OpenAlex
- W2052729994
- Cited by
- 90
- References
- 49
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 15 · 2020: 10 · 2019: 2 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 4
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Naito Foundation
- Takeda Science Foundation
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology (CREST)
- Inamori Foundation
- Japan Society for the Promotion of Science (21229006, 23500399, 23689012)
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Precursory Research for Embryonic Science and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- GluD2, long-term depression, AMPA receptors, GluA2, receptor internalization, Purkinje cells, cerebellum, dephosphorylation, synaptic plasticity
- MeSH terms
- ADP-Ribosylation Factor 6, Animals, Cerebellum, Models, Neurological, Neuronal Plasticity, Phosphorylation, Purkinje Cells, Serine, Tyrosine, Signal Transduction, Receptors, Glutamate, Receptors, AMPA, Mice, Knockout, Patch-Clamp Techniques, Guanine Nucleotide Exchange Factors, ADP-Ribosylation Factors, Protein Subunits, Long-Term Synaptic Depression, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 4, Protein Interaction Domains and Motifs
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