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

ABSTRACT: The death-associated protein kinase 1 (DAPK1) regulates the synaptic movement of the Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII). Synaptic CaMKII accumulation is mediated via binding to the NMDA-receptor subunit GluN2B and is required for long-term potentiation (LTP). By contrast, long-term depression (LTD) instead requires specific suppression of this movement, which is mediated by competitive DAPK1 binding to GluN2B. We find here that DAPK1 localizes to synapses via two distinct mechanisms: basal localization requires F-actin, but retention of DAPK1 at synapses during LTD requires an additional binding mode, likely to GluN2B. While F-actin binding mediates DAPK1 enrichment at synapses, it is not sufficient to suppress synaptic CaMKII movement. However, it is a p

SUBMITTER: Tullis JE 

PROVIDER: S-EPMC10192646 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature