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Cited by 286Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and Signaling

Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating

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Kristensen, Anders S, Jenkins, Meagan A, Banke, Tue G, Schousboe, Arne, Makino, Yuichi, Johnson, Richard C, Huganir, Richard, Traynelis, Stephen F·2011·Nature Neuroscience
DOI 10.1038/nn.2804PMC PMC3102786
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Abstract

The function, trafficking and synaptic signaling of AMPA receptors are tightly regulated by phosphorylation. Ca(2+)/calmodulin-dependent kinase II (CaMKII) phosphorylates the GluA1 AMPA receptor subunit at Ser831 to increase single-channel conductance. We show that CaMKII increases the conductance of native heteromeric AMPA receptors in mouse hippocampal neurons through phosphorylation of Ser831. In addition, co-expression of transmembrane AMPA receptor regulatory proteins (TARPs) with recombinant receptors is required for phospho-Ser831 to increase conductance of heteromeric GluA1-GluA2 receptors. Finally, phosphorylation of Ser831 increases the efficiency with which each subunit can activate, independent of agonist efficacy, thereby increasing the likelihood that more receptor subunits will be simultaneously activated during gating. This underlies the observation that phospho-Ser831 increases the frequency of openings to larger conductances rather than altering unitary conductance. Together, these findings suggest that CaMKII phosphorylation of GluA1-Ser831 decreases the activation energy for an intrasubunit conformational change that regulates the conductance of the receptor when the channel pore opens.

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  • Phosphorylation of S831 of heterologously expressed GluA1 by CaMKII increases single-channel conductance.

    “Phosphorylation of S831 of heterologously expressed GluA1 by CaMKII increases single-channel conductance (267, 268).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [268]

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Authors
Kristensen, A. S., Jenkins, M. A., Banke, T. G., Schousboe, A., Makino, Y., Johnson, R. C., Huganir, R., & Traynelis, S. F.
Affiliations
  • University of Copenhagen (DK)
  • Emory University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Traynelis, Stephen F
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2011-04-24
Volume
14
Issue
6
Pages
727-735
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.2804
PMC
PMC3102786
OpenAlex
W2045780885
Cited by
286
References
5
Citations by year
2026: 12 · 2025: 8 · 2024: 20 · 2023: 26 · 2022: 15 · 2021: 20 · 2020: 21 · 2019: 15 · 2018: 18 · 2017: 19 · 2016: 20 · 2015: 15 · 2014: 28 · 2013: 28 · 2012: 14
FWCI
10.21
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Neurological Disorders and Stroke (R37NS036654, NS068464, R01NS036654, NS036654, R01NS068464)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
CaMKII, TARP, single-channel conductance, hippocampal neurons, receptor trafficking, synaptic signaling
MeSH terms
Animals, Gene Expression Regulation, Hippocampus, Membrane Proteins, Mice, Inbred C57BL, Neurons, Phosphorylation, Serine, Signal Transduction, Receptors, AMPA, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Gene Knock-In Techniques

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