Association of Calcium/Calmodulin-dependent Kinase II with Developmentally Regulated Splice Variants of the Postsynaptic Density Protein Densin-180

Strack, Stefan; Robison, Alfred J.; Bass, Martha A.; Colbran, Roger J.

doi:10.1074/jbc.c000319200

Cited by 95 publications

(145 citation statements)

References 18 publications

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“…Several studies have indicated that αCaMKII autophosphorylation of T286 enhances binding of the kinase to the PSD and several of its constituents (Bayer et al, 2001;Strack et al, 1997b;Strack and Colbran, 1998;Gardoni et al, 1999;Leonard et al, 2002;Strack et al, 2000). In addition, T286 phosphorylation has been shown to decrease the dissociation rate of the kinase from the PSD (Shen et al, 2000;Bayer et al, 2006;Yoshimura and Yamauchi, 1997;Dosemeci et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Aside from promoting Ca 2+ -independent activity of CaMKII, T286 phosphorylation has also been shown to regulate its protein-protein interactions. Phosphorylation of this residue is thought to enhance CaMKII binding to isolated PSDs (Strack et al, 1997b), densin-180 (Strack et al, 2000), and the Nmethyl-D-aspartate receptor (NMDAR) subunits NR2B (Strack and Colbran, 1998;Bayer et al, 2001;Leonard et al, 2002), NR1 (Leonard et al, 2002), and NR2A (Gardoni et al, 1999). Furthermore, T286 phosphorylation has been reported to decrease the dissociation rate of CaMKII that has been bound to the PSD (Shen et al, 2000;Bayer et al, 2006;Yoshimura and Yamauchi, 1997;Dosemeci et al, 2002) (but see (Strack et al, 1997b)).…”

Section: Introductionmentioning

confidence: 99%

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αCaMKII autophosphorylation levels differ depending on subcellular localization

et al. 2007

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Calcium/calmodulin-dependent protein kinase II (CaMKII) has important roles in many processes in the central nervous system. It is enriched at the post-synaptic density (PSD), a localization which is thought to be critical for many of its proposed neuronal functions. In order to better understand the mechanisms that regulate association of CaMKII with the PSD, we compared the levels of autophosphorylation between PSD-associated kinase and kinase in other parts of the neuron. We were surprised to find that αCaMKII in a PSD-enriched fraction prepared from recovered hippocampal CA1-minislices had a relatively low level of threonine 286 (T286) phosphorylation and a relatively high level of threonine 305 (T305) phosphorylation. Furthermore, when the minislices were subjected to a treatment that mimics ischemic conditions, there was a significant translocation of αCaMKII to the PSD-enriched fraction accompanied with a dramatic reduction in T286 phosphorylation levels throughout the neuron. These findings have important implications for our understanding of the role of autophosphorylation in the localization of CaMKII.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

αCaMKII autophosphorylation levels differ depending on subcellular localization

et al. 2007

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“…HSV-GFP and HSV-GFPAC3I have been previously described . For HSV-CaMKII, the cDNA for CaMKIIa was cut from the pcDNA3.1 vector (Strack et al, 2000b) and inserted into the p1005 þ vector using the NheI and BspEI sites. The construct was validated by sequencing.…”

Section: Stereotaxic Surgerymentioning

confidence: 99%

Fluoxetine Epigenetically Alters the CaMKIIα Promoter in Nucleus Accumbens to Regulate ΔFosB Binding and Antidepressant Effects

Robison

Vialou

Sun

et al. 2013

Neuropsychopharmacol

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Chronic social defeat stress in mice produces a susceptible phenotype characterized by several behavioral abnormalities consistent with human depression that are reversed by chronic but not acute exposure to antidepressant medications. Recent work in addiction models demonstrates that the transcription factor DFosB and protein kinase calmodulin-dependent protein kinase II (CaMKII) are co-regulated in nucleus accumbens (NAc), a brain reward region implicated in both addiction and depression models including social defeat. Previous work has also demonstrated that DFosB is induced in NAc after chronic social defeat stress or after chronic antidepressant treatment, wherein it mediates a pro-resilience or antidepressant-like phenotype. Here, using chromatin immunoprecipitation assays, we found that DFosB binds the CaMKIIa gene promoter in NAc and that this binding increases after mice are exposed to chronic social defeat stress. Paradoxically, chronic exposure to the antidepressant fluoxetine reduces binding of DFosB to the CaMKIIa promoter and reduces CaMKII expression in NAc, despite the fact that DFosB is induced under these conditions. These data suggest a novel epigenetic mechanism of antidepressant action, whereby fluoxetine induces some chromatin change at the CaMKIIa promoter, which blocks the DFosB binding. Indeed, chronic fluoxetine reduces acetylation and increases lysine-9 dimethylation of histone H3 at the CaMKIIa promoter in NAc, effects also seen in depressed humans exposed to antidepressants. Overexpression of CaMKII in NAc blocks fluoxetine's antidepressant effects in the chronic social defeat paradigm, whereas inhibition of CaMKII activity in NAc mimics fluoxetine exposure. These findings suggest that epigenetic suppression of CaMKIIa expression in NAc is behaviorally relevant and offer a novel pathway for possible therapeutic intervention in depression and related syndromes.

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“…These findings suggest that other mechanisms of kinase activation are involved in both brain areas. CaM kinase II can be persistently activated by interacting with other proteins, including the NMDA receptor and ether-a-go-go (Eag) K + channel (Strack et al, 2000;Bayer et al, 2001;Sun et al, 2004). These non-canonical mechanisms of activation of CaM kinase II could be a preferential target of antidepressants, because they also seem to be involved at synaptic level (see next section).…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, the kinase autophosphorylation was reduced in synaptosomes from both areas, particularly in HC where up-regulation of Ca 2 + -independent activity was maximal. This suggests that the modulation of CaM kinase II activity by antidepressants at synaptic terminals is independent from autophosphorylation and may involve protein-protein interactions (Strack et al, 2000;Bayer et al, 2001;Sun et al, 2004). Indeed, it has been shown that interaction of CaM kinase II with subunits of the NMDA receptor or the Eag potassium channel activates the kinase independent on autophosphorylation (Bayer et al, 2001;Sun et al, 2004).…”

Section: Chronic Antidepressant Treatments Induce a Redistribution Ofmentioning

confidence: 99%

Chronic Antidepressants Induce Redistribution and Differential Activation of αCaM Kinase II between Presynaptic Compartments

Barbiero

Giambelli

Musazzi

et al. 2007

Neuropsychopharmacol

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Changes in synaptic plasticity are involved in pathophysiology of depression and in the mechanism of antidepressants. Ca 2 + /calmodulin (CaM) kinase II, a protein kinase involved in synaptic plasticity, has been previously shown to be a target of antidepressants. We previously found that antidepressants activate the kinase in hippocampal neuronal cell bodies by increasing phosphorylation at Thr 286 , reduce the kinase phosphorylation in synaptic membranes, and in turn its phosphorylation-dependent interaction with syntaxin-1 and the release of glutamate from hippocampal synaptosomes. Here, we investigated the chronic effect of different antidepressants (fluoxetine, desipramine, and reboxetine) on the expression and function of the kinase in distinct subcellular compartments in order to dissect the different kinase pools affected. Acute treatments did not induce any change in the kinase. In total tissue extracts chronic drug treatments induced activation of the kinase; in hippocampus (HC), but not in prefrontal/frontal cortex, this was partially accounted for by increased Thr 286 phosphorylation, suggesting the involvement of different mechanisms of activation. In synaptosomes, all drugs reduced the kinase phosphorylation, particularly in HC where, upon fractionation of the synaptosomal particulate into synaptic vesicles and membranes, we found that the drugs induced a redistribution and differential activation of the kinase between membranes and vesicles. Furthermore, a large decrease in the level and phosphorylation of synapsin I located at synaptic membranes was consistent with the observed decrease of CaM kinase II. Overall, antidepressants induce a complex pattern of modifications in distinct subcellular compartments; at presynaptic level, these changes are in line with a dampening of glutamate release.

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Association of Calcium/Calmodulin-dependent Kinase II with Developmentally Regulated Splice Variants of the Postsynaptic Density Protein Densin-180

Cited by 95 publications

References 18 publications

αCaMKII autophosphorylation levels differ depending on subcellular localization

αCaMKII autophosphorylation levels differ depending on subcellular localization

Fluoxetine Epigenetically Alters the CaMKIIα Promoter in Nucleus Accumbens to Regulate ΔFosB Binding and Antidepressant Effects

Chronic Antidepressants Induce Redistribution and Differential Activation of αCaM Kinase II between Presynaptic Compartments

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