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Kolodziej S.J., Hudmon A., Waxham M.N., Stoops J.K. Three-dimensional reconstructions of calcium/calmodulin-dependent (CaM) kinase IIα and truncated CaM kinase IIα reveal a unique organization for its structural core and functional domains. J Biol Chem. 275:2000;14354-14359
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The authors present a comparative electron microscopy study of the positions of CaMKII and PSD-95 within isolated PSDs using immunogold labeling, rotary shadowing, and electron microscopic tomography. CaMKII appears in an ordered array on the cytosolic face of PSDs at a mean distance of 25 nm from the synaptic cleft. Although the dimensions of CaMKII towers are consistent with stacking of CaMKII holoenzymes, other proteins might also be present in these structures.
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2+/calmodulin- dependent protein kinase II at the PSD. J Neurosci. 23:2003;11270-11278 The authors present a comparative electron microscopy study of the positions of CaMKII and PSD-95 within isolated PSDs using immunogold labeling, rotary shadowing, and electron microscopic tomography. CaMKII appears in an ordered array on the cytosolic face of PSDs at a mean distance of 25 nm from the synaptic cleft. Although the dimensions of CaMKII towers are consistent with stacking of CaMKII holoenzymes, other proteins might also be present in these structures.
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This is one of the first reports demonstrating CaMKII-isoform selective effects on neurons. CaMKIIβ, but not CaMKIIα, was shown to promote neurite extension in cultured hippocampal neurons. This appears to require specific interaction of CaMKIIβ with F-actin, mediated by an alternatively spliced cassette between the regulatory and the association domains (see Figure 1).
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Fink C.C., Bayer K.U., Myers J.W., Ferrell J.E. Jr., Schulman H., Meyer T. Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII. Neuron. 39:2003;283-297 This is one of the first reports demonstrating CaMKII-isoform selective effects on neurons. CaMKIIβ, but not CaMKIIα, was shown to promote neurite extension in cultured hippocampal neurons. This appears to require specific interaction of CaMKIIβ with F-actin, mediated by an alternatively spliced cassette between the regulatory and the association domains (see Figure 1).
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This is the first study to report that CaMKII translocation to postsynaptic densities occurs in vivo in response to physiological stimulation. The authors express GFP-tagged CaMKIIα in zebrafish and demonstrate reversible translocation to PSDs in vivo in response to repeated sensory stimulation.
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Gleason M.R., Higashijima S., Dallman J., Liu K., Mandel G., Fetcho J.R. Translocation of CaM kinase II to synaptic sites in vivo. Nat Neurosci. 6:2003;217-218 This is the first study to report that CaMKII translocation to postsynaptic densities occurs in vivo in response to physiological stimulation. The authors express GFP-tagged CaMKIIα in zebrafish and demonstrate reversible translocation to PSDs in vivo in response to repeated sensory stimulation.
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Bayer K.U., De Koninck P., Leonard A.S., Hell J.W., Schulman H. Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature. 411:2001;801-805
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This study demonstrates that expression of CaMKII isoforms is differentially regulated by synaptic activity in cultured hippocampal neurons and that the isoforms take distinct functional roles. NMDA receptor activation stimulates CaMKIIα expression, whereas AMPA receptor activation inhibits CaMKIIβ expression. Moreover, CaMKIIβ appears to regulate CaMKIIα expression. Overexpression of CaMKIIα augmented unitary synaptic currents but decreased the frequency of these events, whereas overexpression of CaMKIIβ had opposite effects on synaptic activity.
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Thiagarajan T.C., Piedras-Renteria E.S., Tsien R.W. α- and βCaMKII: inverse regulation by neuronal activity and opposing effects on synaptic strength. Neuron. 36:2002;1103-1114 This study demonstrates that expression of CaMKII isoforms is differentially regulated by synaptic activity in cultured hippocampal neurons and that the isoforms take distinct functional roles. NMDA receptor activation stimulates CaMKIIα expression, whereas AMPA receptor activation inhibits CaMKIIβ expression. Moreover, CaMKIIβ appears to regulate CaMKIIα expression. Overexpression of CaMKIIα augmented unitary synaptic currents but decreased the frequency of these events, whereas overexpression of CaMKIIβ had opposite effects on synaptic activity.
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Havik B., Rokke H., Bardsen K., Davanger S., Bramham C.R. Bursts of high-frequency stimulation trigger rapid delivery of pre-existing alpha-CaMKII mRNA to synapses: a mechanism in dendritic protein synthesis during long-term potentiation in adult awake rats. Eur J Neurosci. 17:2003;2679-2689
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These authors demonstrate that the 3′-UTR of CaMKIIα mRNA is required for dendritic transport in vivo, and for maintenance of normal dendritic CaMKIIα protein levels. This is the first indication that disruption of dendritic, but presumably not somatic, translation of CaMKIIα has significant effects on synaptic plasticity and performance in behavioral tasks.
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Miller S., Yasuda M., Coats J.K., Jones Y., Martone M.E., Mayford M. Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation. Neuron. 36:2002;507-519 These authors demonstrate that the 3′-UTR of CaMKIIα mRNA is required for dendritic transport in vivo, and for maintenance of normal dendritic CaMKIIα protein levels. This is the first indication that disruption of dendritic, but presumably not somatic, translation of CaMKIIα has significant effects on synaptic plasticity and performance in behavioral tasks.
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286 autophosphorylation of CaMKII and increased the amount of CaMKII that co-immunopreciptates with NMDA receptor subunits. These changes were disrupted in mice expressing a truncated PSD-95 protein.
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286 autophosphorylation of CaMKII and increased the amount of CaMKII that co-immunopreciptates with NMDA receptor subunits. These changes were disrupted in mice expressing a truncated PSD-95 protein.
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This study demonstrates that phosphorylation of GluR1 subunits of the AMPA receptor is crucial to normal synaptic plasticity. Transgenic knock-in mice lacking both the CaMKII and the PKA phosphorylation sites in GluR1 subunits of AMPA-type glutamate receptors are shown to exhibit defects in hippocampal synaptic plasticity and spatial learning.
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Lee H.K., Takamiya K., Han J.S., Man H., Kim C.H., Rumbaugh G., Yu S., Ding L., He C., Petralia R.S., et al. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell. 112:2003;631-643 This study demonstrates that phosphorylation of GluR1 subunits of the AMPA receptor is crucial to normal synaptic plasticity. Transgenic knock-in mice lacking both the CaMKII and the PKA phosphorylation sites in GluR1 subunits of AMPA-type glutamate receptors are shown to exhibit defects in hippocampal synaptic plasticity and spatial learning.
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