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CaMKII versus DAPK1 Binding to GluN2B in Ischemic Neuronal Cell Death after Resuscitation from Cardiac Arrest.

Olivia R Buonarati | Sarah G Cook | Dayton J Goodell | Nicholas E Chalmers | Nicole L Rumian | Jonathan E Tullis | Susana Restrepo | Steven J Coultrap | Nidia Quillinan | Paco S Herson | K Ulrich Bayer
Cell reports | 2020

DAPK1 binding to GluN2B was prominently reported to mediate ischemic cell death in vivo. DAPK1 and CaMKII bind to the same GluN2B region, and their binding is mutually exclusive. Here, we show that mutating the binding region on GluN2B (L1298A/R1300Q) protected against neuronal cell death induced by cardiac arrest followed by resuscitation. Importantly, the GluN2B mutation selectively abolished only CaMKII, but not DAPK1, binding. During ischemic or excitotoxic insults, CaMKII further accumulated at excitatory synapses, and this accumulation was mediated by GluN2B binding. Interestingly, extra-synaptic GluN2B decreased after ischemia, but its relative association with DAPK1 increased. Thus, ischemic neuronal death requires CaMKII binding to synaptic GluN2B, whereas any potential role for DAPK1 binding is restricted to a different, likely extra-synaptic population of GluN2B.

Pubmed ID: 31914378

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: F31 AG062160
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS081248
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS080851
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007635
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS092265
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS118786
  • Agency: NIA NIH HHS, United States
    Id: T32 AG000279

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