Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549467 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2017.05.068 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HCN2 promotes neurodevelopmental and synaptic function repair through the CaMKII/CREB pathway to alleviate general anesthesia-induced cognitive impairment.
Cell Signal
September 2025
Department of Anesthesiology and Operation, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, China. Electronic address:
Repeated exposure to gestational general anesthesia during pregnancy has been associated with neurodevelopmental damage and cognitive and social dysfunction in offspring. This study investigates the underlying mechanisms and therapeutic strategies for mitigating these effects. Behavioral tests revealed significant impairments in cognitive, social, and spatial learning abilities in the offspring of general anesthesia-treated mice, alongside delayed eye-opening, reduced body weight, and neuronal damage.
View Article and Find Full Text PDFCa/Calmodulin-Dependent Protein Kinase II (CaMKII)-Targeted Drug Discovery: Challenges and Strategies.
Ageing Res Rev
September 2025
Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, China; Laboratory of Naturel Medicine for drug discovery, School of Pharmacy, China Medical University, Shenyang, 110122, China. Electronic address:
Calcium (Ca)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is an emerging drug target for age-related diseases. It is a multifunctional kinase with complex activation modes, numerous isoforms, broad tissue distribution, and a dual role in health and disease. In particular, its isoforms share a high degree of conservation within the catalytic and regulatory domains, with only minor differences confined to the linker region.
View Article and Find Full Text PDFTauopathies: Calmodulin Regulates Tau Hyperphosphorylation and Its Transformation into Disease-Specific Aggregates.
Biomolecules
August 2025
Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, Canada.
Tauopathies are a diverse group of neurodegenerative diseases characterized by the presence of Tau inclusions in neurons and glia. Rather than the classic steps in the transformation of Tau into neurofibrillary tangles, as first studied in Alzheimer's disease, studies on tauopathies reveal the presence of diverse Tau aggregates that appear to be disease-specific. Regardless, the phosphorylation and hyperphosphorylation of Tau, involving various kinases and phosphatases, appear to be central to all tauopathies.
View Article and Find Full Text PDFCXCL4-Induced PBMCs Modulate Vascular Extracellular Matrix via Wnt5a-Dependent Matrix Metalloproteinase-7 and Calcifying Extracellular Vesicle Release.
Arterioscler Thromb Vasc Biol
August 2025
Department of Cardiology, Pulmonology and Angiology, University Hospital Heidelberg, Germany. (J.B.K., L.K.S., F.S., J.K., C.H., C.A.G., H.A.K., N.F., F.L.).
Background: The role of macrophage heterogeneity has become increasingly well-recognized in the study of vascular inflammatory responses. The CXCL4 (chemokine [C-X-C motif] ligand 4)-induced monocyte/macrophage phenotype has been implicated in atherosclerotic plaque destabilization, a key process preceding plaque rupture. Monocyte-derived macrophages differentiated with CXCL4 exhibit a unique transcriptome characterized by upregulation of S100A8 (S100 calcium-binding protein A8/calgranulin A) and MMP7 (matrix metalloproteinase-7).
View Article and Find Full Text PDFElectroacupuncture activation of the CaMKII/CREB pathway improves dLGN synaptic plasticity in monocular deprivation amblyopic rats.
Neurol Res
August 2025
School of Basic Medical, Wannan Medical College, Wuhu, Anhui, China.
Objective: This study aimed to investigate the therapeutic potential of electroacupuncture(EA) for amblyopia, a common childhood visual disorder caused by early abnormalities such as monocular deprivation(MD). We examined the role of the calcium/calmodulin-dependent protein kinase II/cAMP response element-binding protein(CaMKII/CREB) pathway and enhanced synaptic plasticity in visual function improvement following EA.
Methods: An amblyopia model was established using 14-day-old rats by inducing MD during a critical developmental period.