Selective Regulation of Neurite Extension and Synapse Formation by the β but not the α Isoform of CaMKII

Fink, Charles C.; Bayer, Karl; Myers, Jason W.; Ferrell, James E.; Schulman, Howard; Meyer, Tobias

doi:10.1016/s0896-6273(03)00428-8

Cited by 305 publications

(361 citation statements)

References 59 publications

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“…This may have been represented in our study by the occasional gold particles seen in the cytoplasm but not near the synapse itself. In addition, CaMKIIβ, which is not recognized by our antibody, is very abundant in the brain after birth (mRNA; Bayer et al, 1999), and has been implicated in filopodia extension and synapse formation (Fink et al, 2003). Since CaMKII forms a major portion of the adult PSD, it would not be surprising that similarly structured PSDs at P2 have abundant levels of a developmentally important form of CaMKII, such as CaMKIIβ.…”

Section: Discussionmentioning

confidence: 86%

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

209

196

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In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluRassociated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors and CaMKII. Other components showed more moderate changes.

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Section: Discussionmentioning

confidence: 86%

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

209

196

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“…1B). One of the likely candidates of the ␤ subunit disulfide partner is actin, which has been shown to bind this subunit and is responsible for targeting CaMKII ␣/␤ hetero-oligomers to dendritic spines and in the regulation of neurite extension and synapse formation (44,45). Similarly, although the autophosphorylated ␣ CaMKII is less likely to form self-cluster, due to its increased affinity for several PSD-associated proteins, including NR2B subunit of NMDA receptors (5,16,46), it can form large aggregates containing mixed disulfides (Fig.…”

Section: Discussionmentioning

confidence: 99%

Ischemia-elicited Oxidative Modulation of Ca2+/Calmodulin-dependent Protein Kinase II

Shetty

Huang

2008

Journal of Biological Chemistry

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Ca 2؉ /calmodulin (CaM)-dependent protein kinase II (CaMKII) plays a critical role in neuronal signal transduction and synaptic plasticity. Here, we showed that this kinase was very susceptible to oxidative modulation. Treatment of mouse brain synaptosomes with H 2 O 2 , diamide, and sodium nitroprusside caused aggregation of CaMKII through formation of disulfide and non-disulfide linkages, and partial inhibition of the kinase activity. These CaMKII aggregates were found to associate with the post synaptic density. However, treatment of purified CaMKII with these oxidants did not replicate those effects observed in the synaptosomes. Using two previously identified potential mediators of oxidants in the brain, glutathione disulfide S-monoxide (GS-DSMO) and glutathione disulfide S-dioxide (GS-DSDO), we showed that they oxidized and inhibited CaMKII in a manner partly related to those of the oxidanttreated synaptosomes as well as the ischemia-elicited oxidative stress in the acutely prepared hippocampal slices. Interestingly, the autophosphorylated and activated CaMKII was relatively refractory to GS-DSMO-and GS-DSDO-mediated aggregation. Short term ischemia (10 min) caused a depression of basal synaptic response of the hippocampal slices, and re-oxygenation (after 10 min) reversed the depression. However, oxidation of CaMKII remained at above the pre-ischemic level throughout the treatment. Oxidation of CaMKII also prevented full recovery of CaMKII autophosphorylation after re-oxygenation. Subsequently, the high frequency stimulation-mediated synaptic potentiation in the hippocampal CA1 region was significantly reduced compared with the control without ischemia. Thus, ischemia-evoked oxidation of CaMKII, probably via the action of glutathione disulfide S-oxides or their analogues, may be involved in the suppression of synaptic plasticity.Ca 2ϩ /calmodulin (CaM) 2 -dependent protein kinase II (CaMKII) is one of the major Ca 2ϩ -sensing enzymes important in transducing neuronal, hormonal, and electrical signals in brain, heart, and other tissues. In the central nervous system, CaMKII plays a pivotal role in the facilitation of synaptic plasticity, learning, and memory and in activity-dependent developmental processes (1). CaMKII holoenzyme is a dodecamer composed of two stacked hexameric rings, in which each catalytic/regulatory domain from the upper ring interacts with the equivalent catalytic/regulatory domain in the lower ring by an antiparallel coiled-coil, which resides in regulatory domains (2). Binding of Ca 2ϩ /CaM to the regulatory domain separates the dimer pair and causes the exposure of Thr-286 or Thr-287 (within ␣ or ␤ subunit) for phosphorylation by another catalytic domain in the same ring. This inter-subunit phosphorylation of Thr-286/287 converts the kinase into a high affinity binding protein for Ca 2ϩ /CaM, and the kinase becomes an activatorindependent autonomous enzyme (3). The autophosphorylation also leads to increased affinity of the kinase for several proteins near the sites of elevated Ca 2...

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“…Ca 2ϩ /CaM-dependent kinase II (CaMKII) has been implicated in both activitydependent synaptic strengthening (Lisman et al, 2002) and spine morphogenesis (Fink et al, 2003;Jourdain et al, 2003;Matsuzaki et al, 2004;Narayanan et al, 2006). In dendritic spines, CaMKII is associated with the postsynaptic density (PSD) (Kennedy, 1998;Schulman, 2004) and with the spine cytoskeleton (Shen et al, 1998;Fink et al, 2003;Okamoto et al, 2004). CaMKII is the most abundant protein in the PSD, exceeding in amount even the main structural PSD protein, PSD-95 (Cheng et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Synaptic Strength of Individual Spines Correlates with Bound Ca²⁺–Calmodulin-Dependent Kinase II

Asrican¹,

Lisman²,

Otmakhov³

2007

J. Neurosci.

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Both synaptic strength and spine size vary from spine to spine, but are strongly correlated. This gradation is regulated by activity and may underlie information storage. Ca 2ϩ -calmodulin-dependent kinase II (CaMKII) is critically involved in the regulation of synaptic strength and spine size. The high amount of the kinase in the postsynaptic density has suggested that the kinase has a structural role at synapses. We demonstrated previously that the bound amount of CaMKII␣ in spines persistently increases after induction of long-term potentiation, prompting the hypothesis that this amount may correlate with synaptic strength. To test this hypothesis we combined two recently developed methods, two-photon uncaging of glutamate for determining the EPSC of individual spines (uEPSC) and quantitative microscopy for measuring bound CaMKII␣ in the same spines. We found that under basal conditions the relative bound amount of CaMKII␣ varied over a 10-fold range and positively correlated with the uEPSC. Both the bound amount of CaMKII␣ in spines and uEPSC also positively correlated with spine size. Interestingly, the bound CaMKII␣ fraction (bound/total CaMKII␣ in spines) remained remarkably constant across all spines. The results are consistent with the hypothesis that bound CaMKII serves as a structural organizer of postsynaptic molecules and thereby may be involved in maintaining spine size and synaptic strength.

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Selective Regulation of Neurite Extension and Synapse Formation by the β but not the α Isoform of CaMKII

Cited by 305 publications

References 59 publications

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Ischemia-elicited Oxidative Modulation of Ca2+/Calmodulin-dependent Protein Kinase II

Synaptic Strength of Individual Spines Correlates with Bound Ca²⁺–Calmodulin-Dependent Kinase II

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Selective Regulation of Neurite Extension and Synapse Formation by the β but not the α Isoform of CaMKII

Cited by 305 publications

References 59 publications

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Ischemia-elicited Oxidative Modulation of Ca2+/Calmodulin-dependent Protein Kinase II

Synaptic Strength of Individual Spines Correlates with Bound Ca2+–Calmodulin-Dependent Kinase II

Contact Info

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Synaptic Strength of Individual Spines Correlates with Bound Ca²⁺–Calmodulin-Dependent Kinase II