Ca2+/calmodulin-dependent protein kinases from the neuronal nuclear matrix and post-synaptic density are structurally related.

Maintaining a population of stable synaptic connections is probably of critical importance for the preservation of memories and functional circuitry, but the molecular dynamics that underlie synapse stabilization is poorly understood. Here, we use simultaneous time-lapse imaging of post synaptic density-95 (PSD-95) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) to investigate the dynamics of protein composition at axodendritic (AD) contacts. Our data reveal that this composition is highly dynamic, with both proteins moving into and out of the same synapse independently, so that synapses cycle rapidly between states in which they are enriched for none, one or both proteins. We assessed how PSD-95 and CaMKII interact at stable and transient AD sites and found that both phospho-CaMKII and PSD-95 are present more often at stable than labile contacts. Finally, we found that synaptic contacts are more stable in older neurons, and this process can be mimicked in younger neurons by overexpression of PSD-95. Taken together, these data show that synaptic protein composition is highly variable over a time-scale of hours, and that PSD-95 is probably a key synaptic protein that promotes synapse stability.

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Post-synaptic density-95 promotes calcium/calmodulin-dependent protein kinase II-mediated Ser847 phosphorylation of neuronal nitric oxide synthase

Biochemical Journal ◽

10.1042/bj20030380 ◽

2003 ◽

Vol 372 (2) ◽

pp. 465-471 ◽

Cited By ~ 46

Author(s):

Yasuo WATANABE ◽

Tao SONG ◽

Katsuyoshi SUGIMOTO ◽

Mariko HORII ◽

Nobukazu ARAKI ◽

...

Keyword(s):

Nitric Oxide ◽

Protein Kinase ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Dependent Protein Kinase ◽

Synaptic Density ◽

Transfected Cells ◽

Dependent Protein ◽

Oxide Synthase ◽

Post Synaptic Density

Post-synaptic density-95 (PSD-95) is a neuronal scaffolding protein that associates with N-methyl-d-aspartate (NMDA) receptors and links them to intracellular signalling molecules. In neurons, neuronal nitric oxide synthase (nNOS) binds selectively to the second PDZ domain (PDZ2) of PSD-95, thereby exhibiting physiological activation triggered via NMDA receptors. We have demonstrated previously that Ca2+/calmodulin-dependent protein kinase IIα (CaM-K IIα) directly phosphorylates nNOS at residue Ser847, and can attenuate the catalytic activity of the enzyme in neuronal cells [Komeima, Hayashi, Naito and Watanabe (2000) J. Biol. Chem. 275, 28139–28143]. In the present study, we examined how CaM-K II participates in the phosphorylation by analysing the functional interaction between nNOS and PSD-95 in cells. The results showed that PSD-95 directly promotes the nNOS phosphorylation at Ser847 induced by endogenous CaM-K II. In transfected cells, this effect of PSD-95 required its dual palmitoylation and the PDZ2 domain, but did not rely on its guanylate kinase domain. CaM-K Iα and CaM-K IV failed to phosphorylate nNOS at Ser847 in transfected cells. Thus PSD-95 mediates cellular trafficking of nNOS, and may be required for the efficient phosphorylation of nNOS at Ser847 by CaM-K II in neuronal cells.

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Calcium-Dependent Protein Kinases (CDPK) in Abiotic Stress Tolerance

THE JOURNAL OF PLANT SCIENCE RESEARCH ◽

10.32381/jpsr.2018.34.02.15 ◽

2018 ◽

Vol 34 (2) ◽

pp. 259-265 ◽

Cited By ~ 2

Author(s):

Hemant B Kardile ◽

◽

Vikrant ◽

Nirmal Kant Sharma ◽

Ankita Sharma ◽

...

Keyword(s):

Abiotic Stress ◽

Stress Tolerance ◽

Protein Kinases ◽

Abiotic Stress Tolerance ◽

Calcium Dependent ◽

Dependent Protein ◽

Calcium Dependent Protein Kinases

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Berberine Alleviates Amyloid-beta Pathogenesis Via Activating LKB1/AMPK Signaling in the Brain of APP/PS1 Transgenic Mice

Current Molecular Medicine ◽

10.2174/1566524019666190315164120 ◽

2019 ◽

Vol 19 (5) ◽

pp. 342-348 ◽

Cited By ~ 2

Author(s):

Zhi-You Cai ◽

Chuan-Ling Wang ◽

Tao-Tao Lu ◽

Wen-Ming Yang

Keyword(s):

Transgenic Mice ◽

Western Blotting ◽

Amyloid Β ◽

Adenosine Monophosphate ◽

Camp Response Element Binding ◽

Enzyme Linked Immunosorbent Assay ◽

Synaptic Density ◽

Ampk Signaling ◽

The Brain ◽

Post Synaptic Density

Background:Liver kinase B1 (LKB1)/5’-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer’s disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aβ pathology.Methods:The Aβ levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKβ1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry.Results:BBR inhibited Aβ expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKβ1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice.Conclusion:BBR alleviates Aβ pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.

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