摘要：SummaryBinding 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 GluN2BΔCaMKIImutation (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 GluN2BΔCaMKIImutation 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 resuscitationin vivo. In hippocampal cultures, S1303 phosphorylation was induced by chemical LTD but not LTP stimuli. These results indicate that the additional effect of the GluN2BΔCaMKIImutation on phosphorylation needs to be considered only in LTD but not in LTP or ischemia/excitotoxicity.Graphical abstractDisplay OmittedHighlights•A neuroprotective GluN2B mutation blocked S1303 phosphorylation by CaMKII and DAPK1•GluN2B S1303 is a better substrate for phosphorylation by CaMKII than by DAPK1•Increased phospho-S1303 was detected after cLTD but not cLTP or excitotoxic stimuli•Increased phospho-S1303 was not detected after global cerebral ischemiain vivoBiochemistry; Molecular biology; Neuroscience
