Cited by 97Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNicotinic Acetylcholine Receptors Study

S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis

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Selvakumar, Balakrishnan, Jenkins, Meagan A., Hussain, Natasha K., Huganir, Richard L., Traynelis, Stephen F., Snyder, Solomon H.·2013·Proceedings of the National Academy of Sciences

Abstract

NMDA receptor activation can elicit synaptic plasticity by augmenting conductance of the AMPA receptor GluA1 subsequent to phosphorylation at S831 by Ca 2+ -dependent kinases. NMDA receptor activation also regulates synaptic plasticity by causing endocytosis of AMPA receptor GluA1. We demonstrate a unique signaling cascade for these processes mediated by NMDA receptor-dependent NO formation and GluA1 S-nitrosylation. Thus, S-nitrosylation of GluA1 at C875 enhances S831 phosphorylation, facilitates the associated AMPA receptor conductance increase, and results in endocytosis by increasing receptor binding to the AP2 protein of the endocytotic machinery.

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Crossref · 10.1073/pnas.1221295110

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  • S-nitrosylation of GluA1 C875 by nNOS enhances phosphorylation of GluA1 S831 by CaMKII, suggesting an additional synergistic relationship between S831 phosphorylation and C875 nitrosylation.

    “S-nitrosylation of GluA1 C875 by nNOS was found to enhance the phosphorylation of GluA1 S831 by CaMKII (Figure 1) (Selvakumar et al., 2013), suggesting an additional synergistic relationship between S831 phosphorylation and C875 nitrosylation.”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Selvakumar et al., 2013

    The Results and Discussion report that nNOS-derived NO nitrosylates GluA1 at C875 and facilitates S831 phosphorylation. However, the direct phosphorylation experiments described in the Results used PKC stimulation; the CaMKII experiments measured changes in channel conductance, not a direct enhancement of CaMKII-mediated S831 phosphorylation by C875 nitrosylation. Page numbers were not available in our copy. (LLM, conf=0.85)

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Authors
Selvakumar, B., Jenkins, M. A., Hussain, N. K., Huganir, R. L., Traynelis, S. F., & Snyder, S. H.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Emory University (US)
  • Solomon H. Snyder Department of Neuroscience and Departments of
Venue
Proceedings of the National Academy of Sciences
Published
2012-12-31
Volume
110
Issue
3
Pages
1077-1082
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2106522013
Cited by
97
References
29
Citations by year
2026: 7 · 2025: 3 · 2024: 2 · 2023: 9 · 2022: 4 · 2021: 9 · 2020: 12 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 7
FWCI
3.03
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (R01MH018501, R37MH018501, MH-18501)
  • National Institute of Neurological Disorders and Stroke (NS36715, NS068464, R01NS036715, R01NS068464)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
S-nitrosylation, AMPA receptors, GluR1, NMDA receptor, nitric oxide, receptor phosphorylation, single-channel conductance, receptor internalization, AP-2, synaptic plasticity, calcium signaling
MeSH terms
Animals, Endocytosis, Hippocampus, Humans, Neuronal Plasticity, Neurons, Phosphorylation, Recombinant Proteins, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Mutagenesis, Site-Directed, Receptors, AMPA, Amino Acid Substitution, Nitric Oxide Donors, Mice, Rats, HEK293 Cells

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