GluN2B S1303 Phosphorylation by CaMKII or DAPK1: No Indication for Involvement in Ischemia or LTP

Overview

Journal iScience

Publisher Cell Press

Date 2021 Oct 27

PMID 34704002

Citations 11

Authors

Jonathan E Tullis

Olivia R Buonarati

Steven J Coultrap

Ashley M Bourke

Erika L Tiemeier

Matthew J Kennedy

Paco S Herson

K Ulrich Bayer

Affiliations

Soon will be listed here.

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 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 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 hippocampal cultures, S1303 phosphorylation was induced by chemical LTD but not LTP stimuli. These results indicate that the additional effect of the GluN2B mutation on phosphorylation needs to be considered only in LTD but not in LTP or ischemia/excitotoxicity.

Citing Articles

Induction of LTP mechanisms in dually innervated dendritic spines.

Tullis J, Bayer K Sci Rep. 2024; 14(1):15855.

PMID: 38982271 PMC: 11233660. DOI: 10.1038/s41598-024-66871-8.

The Shank/ProSAP N-Terminal (SPN) Domain of Shank3 Regulates Targeting to Postsynaptic Sites and Postsynaptic Signaling.

Woike D, Tibbe D, Hassani Nia F, Martens V, Wang E, Barsukov I Mol Neurobiol. 2023; 61(2):693-706.

PMID: 37656313 PMC: 10861631. DOI: 10.1007/s12035-023-03611-5.

GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.

Ge Y, Wang Y Front Mol Neurosci. 2023; 16:1190324.

PMID: 37324591 PMC: 10264587. DOI: 10.3389/fnmol.2023.1190324.

Synaptic memory and CaMKII.

Nicoll R, Schulman H Physiol Rev. 2023; 103(4):2877-2925.

PMID: 37290118 PMC: 10642921. DOI: 10.1152/physrev.00034.2022.

Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation.

Tullis J, Bayer K iScience. 2023; 26(5):106723.

PMID: 37216104 PMC: 10192646. DOI: 10.1016/j.isci.2023.106723.

References

Lee H, Kameyama K, Huganir R, Bear M . NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron. 1998; 21(5):1151-62. DOI: 10.1016/s0896-6273(00)80632-7. View

McKay S, Ryan T, McQueen J, Indersmitten T, Marwick K, Hasel P . The Developmental Shift of NMDA Receptor Composition Proceeds Independently of GluN2 Subunit-Specific GluN2 C-Terminal Sequences. Cell Rep. 2018; 25(4):841-851.e4. PMC: 6218242. DOI: 10.1016/j.celrep.2018.09.089. View

Coultrap S, Vest R, Ashpole N, Hudmon A, Bayer K . CaMKII in cerebral ischemia. Acta Pharmacol Sin. 2011; 32(7):861-72. PMC: 3846291. DOI: 10.1038/aps.2011.68. View

Barria A, Malinow R . NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron. 2005; 48(2):289-301. DOI: 10.1016/j.neuron.2005.08.034. View

Sessoms-Sikes S, Honse Y, Lovinger D, Colbran R . CaMKIIalpha enhances the desensitization of NR2B-containing NMDA receptors by an autophosphorylation-dependent mechanism. Mol Cell Neurosci. 2005; 29(1):139-47. DOI: 10.1016/j.mcn.2005.01.006. View

Cook S, Goodell D, Restrepo S, Arnold D, Bayer K . Simultaneous Live Imaging of Multiple Endogenous Proteins Reveals a Mechanism for Alzheimer's-Related Plasticity Impairment. Cell Rep. 2019; 27(3):658-665.e4. PMC: 6482958. DOI: 10.1016/j.celrep.2019.03.041. View

Vieira M, Schmidt J, Ferreira J, She K, Oku S, Mele M . Multiple domains in the C-terminus of NMDA receptor GluN2B subunit contribute to neuronal death following in vitro ischemia. Neurobiol Dis. 2015; 89:223-34. DOI: 10.1016/j.nbd.2015.11.007. View

McQueen J, Ryan T, McKay S, Marwick K, Baxter P, Carpanini S . Pro-death NMDA receptor signaling is promoted by the GluN2B C-terminus independently of Dapk1. Elife. 2017; 6. PMC: 5544426. DOI: 10.7554/eLife.17161. View

Shamloo M, Soriano L, Wieloch T, Nikolich K, Urfer R, Oksenberg D . Death-associated protein kinase is activated by dephosphorylation in response to cerebral ischemia. J Biol Chem. 2005; 280(51):42290-9. DOI: 10.1074/jbc.M505804200. View

10.

Vest R, OLeary H, Coultrap S, Kindy M, Bayer K . Effective post-insult neuroprotection by a novel Ca(2+)/ calmodulin-dependent protein kinase II (CaMKII) inhibitor. J Biol Chem. 2010; 285(27):20675-82. PMC: 2898334. DOI: 10.1074/jbc.M109.088617. View

11.

Barcomb K, Hell J, Benke T, Bayer K . The CaMKII/GluN2B Protein Interaction Maintains Synaptic Strength. J Biol Chem. 2016; 291(31):16082-9. PMC: 4965558. DOI: 10.1074/jbc.M116.734822. View

12.

Lu W, Man H, Ju W, Trimble W, MacDonald J, Wang Y . Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron. 2001; 29(1):243-54. DOI: 10.1016/s0896-6273(01)00194-5. View

13.

Shimizu K, Quillinan N, Orfila J, Herson P . Sirtuin-2 mediates male specific neuronal injury following experimental cardiac arrest through activation of TRPM2 ion channels. Exp Neurol. 2015; 275 Pt 1:78-83. PMC: 5193101. DOI: 10.1016/j.expneurol.2015.10.014. View

14.

Marsden K, Shemesh A, Bayer K, Carroll R . Selective translocation of Ca2+/calmodulin protein kinase IIalpha (CaMKIIalpha) to inhibitory synapses. Proc Natl Acad Sci U S A. 2010; 107(47):20559-64. PMC: 2996683. DOI: 10.1073/pnas.1010346107. View

15.

Velentza A, Wainwright M, Zasadzki M, Mirzoeva S, Schumacher A, Haiech J . An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Bioorg Med Chem Lett. 2003; 13(20):3465-70. DOI: 10.1016/s0960-894x(03)00733-9. View

16.

Coultrap S, Buard I, Kulbe J, DellAcqua M, Bayer K . CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin. J Biol Chem. 2010; 285(23):17930-7. PMC: 2878555. DOI: 10.1074/jbc.M109.069351. View

17.

Kennelly P, KREBS E . Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991; 266(24):15555-8. View

18.

Goodell D, Zaegel V, Coultrap S, Hell J, Bayer K . DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific. Cell Rep. 2017; 19(11):2231-2243. PMC: 5549467. DOI: 10.1016/j.celrep.2017.05.068. View

19.

Liao D, Scannevin R, Huganir R . Activation of silent synapses by rapid activity-dependent synaptic recruitment of AMPA receptors. J Neurosci. 2001; 21(16):6008-17. PMC: 6763128. View

20.

Buonarati O, Cook S, Goodell D, Chalmers N, Rumian N, Tullis J . CaMKII versus DAPK1 Binding to GluN2B in Ischemic Neuronal Cell Death after Resuscitation from Cardiac Arrest. Cell Rep. 2020; 30(1):1-8.e4. PMC: 6959131. DOI: 10.1016/j.celrep.2019.11.076. View