GluN2B S1303 phosphorylation by CaMKII or DAPK1: No indication for involvement in ischemia or LTP
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
Jonathan E. Tullis
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Olivia R. Buonarati
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Steven J. Coultrap
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Ashley M. Bourke
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Erika L. Tiemeier
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Matthew J. Kennedy
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Paco S. Herson
Department 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 author
K. Ulrich Bayer
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding author
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.
