Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Heterosynaptic molecular dynamics: locally induced propagating synaptic accumulation of CaM kinase II.

ABSTRACT: Calcium-calmodulin-dependent protein kinase II (CaMKII) is a key mediator of synaptic plasticity and learning. Global pyramidal cell glutamate stimulation induces translocation of CaMKII from dendritic shafts to spines. Here we show that local dendritic stimulation by puffing glutamate onto a region containing 7-32 synapses induces translocation of CaMKII to synapses initially at the puff site but that translocation subsequently spreads within dendrites to the distal dendrite arbor, resulting in a persistent, widespread synaptic accumulation. This locally induced propagating synaptic (L-IPS) accumulation of CaMKII requires activation of NMDA receptors and L-type Ca(2+) channels and is preceded by a Ca(2+) spike. L-IPS translocation of CaMKII alters biochemical signaling and is associated with an increase in AMPA receptor GluR1 at both stimulated and nonstimulated synapses and thus provides a molecular mechanism for heterosynaptic plasticity.

SUBMITTER: Rose J

PROVIDER: S-EPMC2677100 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Heterosynaptic molecular dynamics: locally induced propagating synaptic accumulation of CaM kinase II.

Rose Jacqueline J Jin Shan-Xue SX Craig Ann Marie AM

Neuron 20090201 3

Calcium-calmodulin-dependent protein kinase II (CaMKII) is a key mediator of synaptic plasticity and learning. Global pyramidal cell glutamate stimulation induces translocation of CaMKII from dendritic shafts to spines. Here we show that local dendritic stimulation by puffing glutamate onto a region containing 7-32 synapses induces translocation of CaMKII to synapses initially at the puff site but that translocation subsequently spreads within dendrites to the distal dendrite arbor, resulting in ...[more]

PMID: 19217373

Similar Datasets

Infrared inhibition impacts on locally initiated and propagating action potentials and the downstream synaptic transmission.

Project description:Significance: Systematic studies of the physiological outputs induced by infrared (IR)-mediated inhibition of motor nerves can provide guidance for therapeutic applications and offer critical insights into IR light modulation of complex neural networks. Aim: We explore the IR-mediated inhibition of action potentials (APs) that either propagate along single axons or are initiated locally and their downstream synaptic transmission responses. Approach: APs were evoked locally by two-electrode current clamp or at a distance for propagating APs. The neuromuscular transmission was recorded with intracellular electrodes in muscle cells or macro-patch pipettes on terminal bouton clusters. Results: IR light pulses completely and reversibly terminate the locally initiated APs firing at low frequencies, which leads to blocking of the synaptic transmission. However, IR light pulses only suppress but do not block the amplitude and duration of propagating APs nor locally initiated APs firing at high frequencies. Such suppressed APs do not influence the postsynaptic responses at a distance. While the suppression of AP amplitude and duration is similar for propagating and locally evoked APs, only the former exhibits a 7% to 21% increase in the maximum time derivative of the AP rising phase. Conclusions: The suppressed APs of motor axons can resume their waveforms after passing the localized IR light illumination site, leaving the muscular and synaptic responses unchanged. IR-mediated modulation on propagating and locally evoked APs should be considered as two separate models for axonal and somatic modulations.

| S-EPMC7554448 | biostudies-literature

Beta Ca2+/CaM-dependent kinase type II triggers upregulation of GluA1 to coordinate adaptation to synaptic inactivity in hippocampal neurons.

Project description:Prolonged AMPA-receptor blockade in hippocampal neuron cultures leads to both an increased expression of GluA1 postsynaptically and an increase in vesicle pool size and turnover rate presynaptically, adaptive changes that extend beyond simple synaptic scaling. As a molecular correlate, expression of the β Ca(2+)/CaM-dependent kinase type II (βCaMKII) is increased in response to synaptic inactivity. Here we set out to clarify the role of βCaMKII in the various manifestations of adaptation. Knockdown of βCaMKII by lentiviral-mediated expression of shRNA prevented the synaptic inactivity-induced increase in GluA1, as did treatment with the CaM kinase inhibitor KN-93, but not the inactive analog KN-92. These results demonstrate that, spurred by AMPA-receptor blockade, up-regulation of βCaMKII promotes increased GluA1 expression. Indeed, transfection of βCaMKII, but not a kinase-dead mutant, increased GluA1 expression on dendrites and elevated vesicle turnover (Syt-Ab uptake), mimicking the effect of synaptic inactivity on both sides of the synapse. In cells with elevated βCaMKII, relief of synaptic-activity blockade uncovered an increase in the frequency of miniature excitatory postsynaptic currents that could be rapidly and fully suppressed by PhTx blockade of GluA1 receptors. This increased mini frequency involved a genuine presynaptic enhancement, not merely an increased abundance of synapses. This finding suggests that Ca(2+) flux through GluA1 receptors may trigger the acute release of a retrograde messenger. Taken together, our results indicate that synaptic inactivity-induced increases in βCaMKII expression set in motion a series of events that culminate in coordinated pre- and postsynaptic adaptations in synaptic transmission.

| S-EPMC3021030 | biostudies-literature

Dissecting cooperative calmodulin binding to CaM kinase II: a detailed stochastic model.

Project description:Calmodulin (CaM) is a major Ca(2+) binding protein involved in two opposing processes of synaptic plasticity of CA1 pyramidal neurons: long-term potentiation (LTP) and depression (LTD). The N- and C-terminal lobes of CaM bind to its target separately but cooperatively and introduce complex dynamics that cannot be well understood by experimental measurement. Using a detailed stochastic model constructed upon experimental data, we have studied the interaction between CaM and Ca(2+)-CaM-dependent protein kinase II (CaMKII), a key enzyme underlying LTP. The model suggests that the accelerated binding of one lobe of CaM to CaMKII, when the opposing lobe is already bound to CaMKII, is a critical determinant of the cooperative interaction between Ca(2+), CaM, and CaMKII. The model indicates that the target-bound Ca(2+) free N-lobe has an extended lifetime and may regulate the Ca(2+) response of CaMKII during LTP induction. The model also reveals multiple kinetic pathways which have not been previously predicted for CaM-dissociation from CaMKII.

| S-EPMC3617043 | biostudies-literature

Retinal ganglion cells expressing CaM kinase II in human and nonhuman primates.

Project description:Immunoreactivity for calcium-/calmodulin-dependent protein kinase II (CaMKII) in the primate dorsal lateral geniculate nucleus (dLGN) has been attributed to geniculocortical relay neurons and has also been suggested to arise from terminals of retinal ganglion cells. Here, we combined immunostaining with single-cell injections to investigate the expression of CaMKII in retinal ganglion cells of three primate species: macaque (Macaca fascicularis, M. nemestrina), human, and marmoset (Callithrix jacchus). We found that in all species, about 2%-10% of the total ganglion cell population expressed CaMKII. In all species, CaMKII was expressed by multiple types of wide-field ganglion cell including large sparse, giant sparse (melanopsin-expressing), broad thorny, and narrow thorny cells. Three other ganglion cells types, namely, inner and outer stratifying maze cells in macaque and tufted cells in marmoset were also found. Double labeling experiments showed that CaMKII-expressing cells included inner and outer stratifying melanopsin cells. Nearly all CaMKII-expressing ganglion cell types identified here are known to project to the koniocellular layers of the dLGN as well as to the superior colliculus. The best characterized koniocellular projecting cell type-the small bistratified (blue ON/yellow OFF) cell-was, however, not CaMKII-positive in any species. Our results indicate that the pattern of CaMKII expression in retinal ganglion cells is largely conserved across different species of primate suggesting a common functional role. But the results also show that CaMKII is not a marker for all koniocellular projecting retinal ganglion cells.

| S-EPMC9010361 | biostudies-literature

Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex.

Project description:Neuronal activity augments maturation of mushroom-shaped spines to form excitatory synapses, thereby strengthening synaptic transmission. We have delineated a Ca(2+)-signaling pathway downstream of the NMDA receptor that stimulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and synapses in hippocampal neurons. CaMKK and CaMKI form a multiprotein signaling complex with the guanine nucleotide exchange factor (GEF) betaPIX and GIT1 that is localized in spines. CaMKI-mediated phosphorylation of Ser516 in betaPIX enhances its GEF activity, resulting in activation of Rac1, an established enhancer of spinogenesis. Suppression of CaMKK or CaMKI by pharmacological inhibitors, dominant-negative (dn) constructs and siRNAs, as well as expression of the betaPIX Ser516Ala mutant, decreases spine formation and mEPSC frequency. Constitutively-active Pak1, a downstream effector of Rac1, rescues spine inhibition by dnCaMKI or betaPIX S516A. This activity-dependent signaling pathway can promote synapse formation during neuronal development and in structural plasticity.

| S-EPMC2277504 | biostudies-literature

CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation.

Project description:Sympathetic activation of ?-adrenoreceptors (?-AR) represents a hallmark in the development of heart failure (HF). However, little is known about the underlying mechanisms of gene regulation. In human ventricular myocardium from patients with end-stage HF, we found high levels of phosphorylated histone 3 at serine-28 (H3S28p). H3S28p was increased by inhibition of the catecholamine-sensitive protein phosphatase 1 and decreased by ?-blocker pretreatment. By a series of in vitro and in vivo experiments, we show that the ?-AR downstream protein kinase CaM kinase II (CaMKII) directly binds and phosphorylates H3S28. Whereas, in CaMKII-deficient myocytes, acute catecholaminergic stimulation resulted in some degree of H3S28p, sustained catecholaminergic stimulation almost entirely failed to induce H3S28p. Genome-wide analysis of CaMKII-mediated H3S28p in response to chronic ?-AR stress by chromatin immunoprecipitation followed by massive genomic sequencing led to the identification of CaMKII-dependent H3S28p target genes. Forty percent of differentially H3S28p-enriched genomic regions were associated with differential, mostly increased expression of the nearest genes, pointing to CaMKII-dependent H3S28p as an activating histone mark. Remarkably, the adult hemoglobin genes showed an H3S28p enrichment close to their transcriptional start or end sites, which was associated with increased messenger RNA and protein expression. In summary, we demonstrate that chronic ?-AR activation leads to CaMKII-mediated H3S28p in cardiomyocytes. Thus, H3S28p-dependent changes may play an unexpected role for cardiac hemoglobin regulation in the context of sympathetic activation. These data also imply that CaMKII may be a yet unrecognized stress-responsive regulator of hematopoesis.

| S-EPMC6825262 | biostudies-literature

Long-term potentiation-dependent spine enlargement requires synaptic Ca2+-permeable AMPA receptors recruited by CaM-kinase I.

Project description:It is well established that long-term potentiation (LTP), a paradigm for learning and memory, results in a stable enlargement of potentiated spines associated with recruitment of additional GluA1-containing AMPA receptors (AMPARs). Although regulation of the actin cytoskeleton is involved, the detailed signaling mechanisms responsible for this spine expansion are unclear. Here, we used cultured mature hippocampal neurons stimulated with a glycine-induced, synapse-specific form of chemical LTP (GI-LTP). We report that the stable structural plasticity (i.e., spine head enlargement and spine length shortening) that accompanies GI-LTP was blocked by inhibitors of NMDA receptors (NMDARs; APV) or CaM-kinase kinase (STO-609), the upstream activator of CaM-kinase I (CaMKI), as well as by transfection with dominant-negative (dn) CaMKI but not dnCaMKIV. Recruitment of GluA1 to the spine surface occurred after GI-LTP and was mimicked by transfection with constitutively active CaMKI. Spine enlargement induced by transfection of GluA1 was associated with synaptic recruitment of Ca(2+)-permeable AMPARs (CP-AMPARs) as assessed by an increase in the rectification index of miniature EPSCs (mEPSCs) and their sensitivity to IEM-1460, a selective antagonist of CP-AMPARs. Furthermore, the increase in spine size and mEPSC amplitude resulting from GI-LTP itself was blocked by IEM-1460, demonstrating involvement of CP-AMPARs. Downstream signaling effectors of CP-AMPARs, identified by suppression of their activation by IEM-1460, included the Rac/PAK/LIM-kinase pathway that regulates spine actin dynamics. Together, our results suggest that synaptic recruitment of CP-AMPARs via CaMKI may provide a mechanistic link between NMDAR activation in LTP and regulation of a signaling pathway that drives spine enlargement via actin polymerization.

| S-EPMC2943838 | biostudies-literature

CaM kinase II delta2-dependent regulation of vascular smooth muscle cell polarization and migration.

Project description:Previous studies indicate involvement of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) in vascular smooth muscle (VSM) cell migration. In the present study, molecular loss-of-function studies were used specifically to assess the role of the predominant CaMKII delta2 isoform on VSM cell migration using a scratch wound healing assay. Targeted CaMKII delta2 knockdown using siRNA or inhibition of activity by overexpressing a kinase-negative mutant resulted in attenuation of VSM cell migration. Temporal and spatial assessments of kinase autophosphorylation indicated rapid and transient activation in response to wounding, in addition to a sustained activation in the leading edge of migrating and spreading cells. Furthermore, siRNA-mediated suppression of CaMKII delta2 resulted in the inhibition of wound-induced Rac activation and Golgi reorganization, and disruption of leading edge morphology, indicating an important function for CaMKII delta2 in regulating VSM cell polarization. Numerous previous reports link activation of CaMKII to ERK1/2 signaling in VSM. Wound-induced ERK1/2 activation was also found to be dependent on CaMKII; however, ERK activity did not account for effects of CaMKII in regulating Golgi polarization, indicating alternative mechanisms by which CaMKII affects the complex events involved in cell migration. Wounding a VSM cell monolayer results in CaMKII delta2 activation, which positively regulates VSM cell polarization and downstream signaling, including Rac and ERK1/2 activation, leading to cell migration.

| S-EPMC3689296 | biostudies-literature

CaM kinase II in colonic smooth muscle contributes to dysmotility in murine DSS-colitis.

Project description:BackgroundAltered calcium mobilization has been implicated in the development of colonic dysmotility in inflammatory bowel disease. The aim of this study was to investigate the mechanisms by which disrupted intracellular Ca(2+) signalling contributes to the impaired contractility of colon circular smooth muscles.MethodsAcute colitis was induced in C57Bl/6 mice with dextran sulphate sodium (DSS) in the drinking water for 5 days.Key resultsSpontaneous and acetylcholine-evoked contractions, caffeine-evoked hyperpolarization, and SERCA2 and phospholamban expression were reduced compared with controls. Tetrodotoxin did not restore control levels of contractile activity. The amplitudes, but not the frequency, of intracellular Ca(2+) waves were increased compared with controls. Caffeine abolished intracellular Ca(2+) waves in control smooth muscle cells, but not in smooth muscle cells from DSS-treated mice. CaM kinase II activity and cytosolic levels of HDAC4 were increased, and I kappaB alpha levels were decreased in distal colon smooth muscles from DSS-treated mice.Conclusions & inferencesThese results suggest that disruptions in intracellular Ca(2+) mobilization due to down-regulation of SERCA2 and phospholamban expression lead to increased CaM kinase II activity and cytosolic HDAC4 that may contribute to the dysmotility of colonic smooth muscles in colitis by enhancing NF-kappaB activity.

| S-EPMC2806503 | biostudies-literature

CaM Kinase II mediates maladaptive post-infarct remodeling but not acute myocardial ischemia/reperfusion injury

Project description:Calcium/calmodulin-dependent protein kinase II (CaMKII) was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. However, the specific functions of the CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury have not been investigated yet. Thus, we studied the roles of the CaMKII isoforms and splice variants in I/R by the use of various CaMKII mutant mice. CaMKIIÎ´C was up-regulated already one day after I/R injury but surprisingly, acute I/R injury was neither affected in CaMKIIÎ´-deficient mice, CaMKIIÎ´-deficient mice in which the splice variants CaMKIIÎ´B and C were re-expressed nor in conditional CaMKIIÎ´/Î³ double-knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction. Leukocyte infiltration was not altered one day but five days after I/R, explaining the late effects of CaMKII deletion on post-I/R remodeling. Other than reported before, we demonstrate that CaMKII is not critically involved in the immediate mechanisms that regulate acute I/R injury but in the process of post-infarct remodeling. We analysed 6 groups in total: 3 groups from wild-type control animals and 3 groups from CaMKII delta/gamma double-KO mice. Sham operated animals served as controls in both wild-type and KO animal groups. 2 different time points in ischia/reperfusion operated animals were investigated: 1 day and 5 days post-surgery.

2014-09-08 | E-GEOD-58486 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data