Fig. 6
From: Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease
The role of DAPK1 in regulating synaptic functions. a DAPK1 is enriched in neuronal synapses, and is physiologically involved in the modulation of synaptic plasticity by interacting with the GluN2B subunit of NMDAR. During LTP, high levels of Ca2+/CaM suppress the DAPK1-induced phosphorylation of GluN2B, which then facilitates the binding between CaMKII and NMDAR and potentiates LTP formation. However, in LTD, DAPK1 is activated by calcineurin-mediated dephosphorylation of Ser308 residue, leading to an upregulation of GluN2B phosphorylation at Ser1303 that is necessary for the formation of LTD. b It has also been reported that DAPK1 is hyperactivated in the hippocampus during brain ageing. The activation of DAPK1 results in caspase-3-dependent Caytaxin degradation in presynapses, further affecting synaptic neurotransmission and the formation of LTP