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Cited by 13Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismTreatment of Major Depression

GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP

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Tullis, Jonathan E., Buonarati, Olivia R., Coultrap, Steven J., Bourke, Ashley M., Tiemeier, Erika L., Kennedy, Matthew J., Herson, Paco S., Bayer, K. Ulrich·2021·iScience
DOI 10.1016/j.isci.2021.103214PMC PMC8524186
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Abstract

Binding of two different CaM kinases, CaMKII and DAPK1, to the NMDA-type glutamate receptor (NMDAR) subunit GluN2B near S1303 has been implicated in excitotoxic/ischemic neuronal cell death. The GluN2B ΔCaMKII mutation (L1298A, R1300Q) is neuroprotective but abolishes only CaMKII but not DAPK1 binding. However, both kinases can additionally phosphorylate GluN2B S1303. Thus, we here tested S1303 phosphorylation for possible contribution to neuronal cell death. The GluN2B ΔCaMKII mutation completely abolished phosphorylation by CaMKII and DAPK1, suggesting that the mutation could mediate neuroprotection by disrupting phosphorylation. However, S1303 phosphorylation was not increased by excitotoxic insults in hippocampal slices or by global cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation in vivo . In hippocampal cultures, S1303 phosphorylation was induced by chemical LTD but not LTP stimuli. These results indicate that the additional effect of the GluN2B ΔCaMKII mutation on phosphorylation needs to be considered only in LTD but not in LTP or ischemia/excitotoxicity.

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  • Disrupting CaMKII binding prevents S1303 phosphorylation.

    “Disrupting CaMKII binding prevents phosphorylation (124).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [124]

    The Results section reports that the GluN2BΔCaMKII mutation abolishes S1303 phosphorylation by CaMKII, and the Discussion says the mutation abolishes both CaMKII binding and S1303 phosphorylation. The paper does not establish that loss of binding itself prevents phosphorylation; it treats these as two effects of the mutation. (LLM, conf=0.84)

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Authors
Tullis, J. E., Buonarati, O. R., Coultrap, S. J., Bourke, A. M., Tiemeier, E. L., Kennedy, M. J., Herson, P. S., & Bayer, K. U.
Affiliations
University of Colorado Anschutz (US)
Corresponding author
  • Herson, Paco S.
  • Bayer, K. Ulrich
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2021-10
Volume
24
Issue
10
Pages
103214
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2021.103214
PMC
PMC8524186
OpenAlex
W3203175700
Cited by
13
References
3
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 5
FWCI
1.27
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (F32AG066536, R01AG067713, R01NS081248, R01NS110383, R01NS118786, T32GM007635)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
GluN2B, CaMKII, DAPK1, NMDA receptor, neuroprotection, global cerebral ischemia, hippocampal slices, long-term depression, long-term potentiation, calcium/calmodulin-dependent protein kinase

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