Cited by 62Neuroscience and Neuropharmacology ResearchTreatment of Major DepressionAmino Acid Enzymes and Metabolism

NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840

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Delgado, Jary Y., Coba, Marcelo, Anderson, Christopher N. G., Thompson, Kimberly R., Gray, Erin E., Heusner, Carrie L., Martin, Kelsey C., Grant, Seth G. N. +1 more·2007·The Journal of Neuroscience

Abstract

Phosphorylation-dependent changes in AMPA receptor function have a crucial role in activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD). Although three previously identified phosphorylation sites in AMPA receptor glutamate receptor 1 (GluR1) subunits (S818, S831, and S845) appear to have important roles in LTP and LTD, little is known about the role of other putative phosphorylation sites in GluR1. Here, we describe the characterization of a recently identified phosphorylation site in GluR1 at threonine 840. The results of in vivo and in vitro phosphorylation assays suggest that T840 is not a substrate for protein kinases known to phosphorylate GluR1 at previously identified phosphorylation sites, such as protein kinase A, protein kinase C, and calcium/calmodulin-dependent kinase II. Instead, in vitro phosphorylation assays suggest that T840 is a substrate for p70S6 kinase. Although LTP-inducing patterns of synaptic stimulation had no effect on GluR1 phosphorylation at T840 in the hippocampal CA1 region, bath application of NMDA induced a strong, protein phosphatase 1- and/or 2A-mediated decrease in T840 phosphorylation. Moreover, GluR1 phosphorylation at T840 was transiently decreased by a chemical LTD induction protocol that induced a short-term depression of synaptic strength and persistently decreased by a chemical LTD induction protocol that induced a lasting depression of synaptic transmission. Together, our results show that GluR1 phosphorylation at T840 is regulated by NMDA receptor activation and suggest that decreases in GluR1 phosphorylation at T840 may have a role in LTD.

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Crossref · 10.1523/jneurosci.3056-07.2007

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  • During LTD, GluA1 T840 is dephosphorylated by PP1/PP2A and S845 by CaN.

    “GluA1 undergoes dephosphorylation of T840 and S845 during LTD by protein phosphatases PP1/PP2A and CaN, respectively (Delgado et al., 2007, Toda and Huganir, 2015, Lee et al., 1998, Sanderson et al., 2016).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Delgado et al., 2007

    The Results sections on chem-LTD and T840 phosphatases report persistent T840 dephosphorylation during chemical LTD and show that inhibiting PP1/PP2A prevents NMDA-induced T840 dephosphorylation. They do not establish the same change during synaptically induced LTD, and the paper does not identify CaN as the phosphatase responsible for S845 dephosphorylation. (LLM, conf=0.87)

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Authors
Delgado, J. Y., Coba, M., Anderson, C. N. G., Thompson, K. R., Gray, E. E., Heusner, C. L., Martin, K. C., Grant, S. G. N., & O'Dell, T. J.
Affiliations
  • University of California, Los Angeles (US)
  • Wellcome Sanger Institute (GB)
Venue
The Journal of Neuroscience
Published
2007-11-28
Volume
27
Issue
48
Pages
13210-13221
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2036834190
Cited by
62
References
46
Citations by year
2026: 1 · 2025: 3 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 8 · 2012: 1
FWCI
1.73
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • W. M. Keck Foundation
  • National Alliance for Research on Schizophrenia and Depression
  • Wellcome Trust (077155)
  • National Institute of Mental Health (R01MH060919)
  • Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
AMPA receptors, GluR1, phosphorylation, NMDA receptor activation, dephosphorylation, protein phosphatase 1, protein phosphatase 2A, p70 S6 kinase, long-term depression, long-term potentiation, synaptic plasticity, hippocampal CA1
MeSH terms
Adrenergic beta-Agonists, Analysis of Variance, Animals, Cells, Cultured, Enzyme Inhibitors, Colforsin, Hippocampus, Humans, Isoproterenol, Mice, Inbred C57BL, Neurons, Threonine, Transfection, Receptors, N-Methyl-D-Aspartate, Mutagenesis, Long-Term Potentiation, Receptors, AMPA, Excitatory Amino Acid Agents, Excitatory Postsynaptic Potentials, Protein Array Analysis, Mice, In Vitro Techniques

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