GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP
Summary: 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 GluN2BΔCaMKII mutation (L1298A, R1300Q) is neuroprotective but abolishes only CaMKII but not DAP...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221011822 |
| _version_ | 1818581376594608128 |
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| author | Jonathan E. Tullis Olivia R. Buonarati Steven J. Coultrap Ashley M. Bourke Erika L. Tiemeier Matthew J. Kennedy Paco S. Herson K. Ulrich Bayer |
| author_facet | Jonathan E. Tullis Olivia R. Buonarati Steven J. Coultrap Ashley M. Bourke Erika L. Tiemeier Matthew J. Kennedy Paco S. Herson K. Ulrich Bayer |
| author_sort | Jonathan E. Tullis |
| collection | DOAJ |
| description | Summary: 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 GluN2BΔCaMKII 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 GluN2BΔCaMKII 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 GluN2BΔCaMKII mutation on phosphorylation needs to be considered only in LTD but not in LTP or ischemia/excitotoxicity. |
| first_indexed | 2024-12-16T07:32:31Z |
| format | Article |
| id | doaj.art-f415611452a44fc8862991682f4e7cfa |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T07:32:31Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f415611452a44fc8862991682f4e7cfa2022-12-21T22:39:18ZengElsevieriScience2589-00422021-10-012410103214GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTPJonathan E. Tullis0Olivia R. Buonarati1Steven J. Coultrap2Ashley M. Bourke3Erika L. Tiemeier4Matthew J. Kennedy5Paco S. Herson6K. Ulrich Bayer7Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding authorDepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding authorSummary: 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 GluN2BΔCaMKII 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 GluN2BΔCaMKII 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 GluN2BΔCaMKII mutation on phosphorylation needs to be considered only in LTD but not in LTP or ischemia/excitotoxicity.http://www.sciencedirect.com/science/article/pii/S2589004221011822BiochemistryMolecular biologyNeuroscience |
| spellingShingle | Jonathan E. Tullis Olivia R. Buonarati Steven J. Coultrap Ashley M. Bourke Erika L. Tiemeier Matthew J. Kennedy Paco S. Herson K. Ulrich Bayer GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP iScience Biochemistry Molecular biology Neuroscience |
| title | GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP |
| title_full | GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP |
| title_fullStr | GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP |
| title_full_unstemmed | GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP |
| title_short | GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP |
| title_sort | glun2b s1303 phosphorylation by camkii or dapk1 no indication for involvement in ischemia or ltp |
| topic | Biochemistry Molecular biology Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221011822 |
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