Transition from Reversible to Persistent Binding of CaMKII to Postsynaptic Sites and NR2B

Bayer, K. Ulrich; Lebel, Estelle; McDonald, Greg L.; O’Leary, Heather; Schulman, Howard; Koninck, Paul De

doi:10.1523/jneurosci.3116-05.2006

Cited by 220 publications

(319 citation statements)

References 60 publications

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“…Support for this conclusion can also be found in work showing that αCaMKII in which T286 has been mutated to alanine can still translocate to (Shen and Meyer, 1999;Bayer et al, 2001) and be constitutively localized at the synapse (Bayer et al, 2006), and αCaMKII in which T286 has been mutated to aspartate still requires neuronal activation to initially translocate to the PSD (Shen et al, 2000). Clearly, much remains to be elucidated regarding the localization and trafficking of CaMKII to the post-synaptic density.…”

Section: Discussionmentioning

confidence: 80%

“…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). It has also been observed that autophosphorylation of T305/6 inhibits binding of αCaMKII to the PSD and several PSD proteins (Strack et al, 1997b;Leonard et al, 2002;Robison et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…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)). These studies suggest that phosphorylation of T286 is an important regulatory mechanism controlling αCaMKII association with the PSD, and that PSD-associated αCaMKII is most likely more heavily phosphorylated on T286 than αCaMKII in other parts of the neuron.…”

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: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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αCaMKII autophosphorylation levels differ depending on subcellular localization

et al. 2007

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“…␣CaMKII translocation into spines after global chemical stimulation has been demonstrated previously (8,24,25). Here, our question was whether ␣CaMKII translocation is detectable, specific, and persistent following potentiation of a single synapse.…”

Section: Spine Enlargement Precedes the Input-specific Accumulation Ofmentioning

confidence: 80%

Optical induction of plasticity at single synapses reveals input-specific accumulation of αCaMKII

Zhang

Holbro²,

Oertner³

2008

Proc. Natl. Acad. Sci. U.S.A.

125

113

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Long-term potentiation (LTP), a form of synaptic plasticity, is a primary experimental model for understanding learning and memory formation. Here, we use light-activated channelrhodopsin-2 (ChR2) as a tool to study the molecular events that occur in dendritic spines of CA1 pyramidal cells during LTP induction. Two-photon uncaging of MNI-glutamate allowed us to selectively activate excitatory synapses on optically identified spines while ChR2 provided independent control of postsynaptic depolarization by blue light. Pairing of these optical stimuli induced lasting increase of spine volume and triggered translocation of ␣CaMKII to the stimulated spines. No changes in ␣CaMKII concentration or cytoplasmic volume were observed in neighboring spines on the same dendrite, providing evidence that ␣CaMKII accumulation at postsynaptic sites is a synapse-specific memory trace of coincident activity.channelrhodopsin-2 ͉ dendritic spines ͉ synaptic plasticity ͉ two-photon uncaging ͉ MNI-glutamate A ctivity-dependent changes in synaptic strength are generally considered to be the cellular basis of learning and memory (1). Long-term potentiation (LTP), the most extensively studied form of such synaptic plasticity, can be triggered within seconds by coincident activity in presynaptic and postsynaptic cells. The possible structural modifications that occur at synapses where LTP has been induced are poorly known because of the difficulty of simultaneously measuring functional and morphological parameters at individual synapses. Furthermore, it is controversial whether neighboring synapses can be modified independently (2-4). In a recent report, it has been shown that spatially clustered synapses can cooperate in the induction of plasticity and that cytoplasmic factors are responsible for this functional cross-talk (5). The identity of these diffusible factors, however, has not been clarified.A key player in the LTP signaling cascade is ␣CaMKII, which is thought to function as a molecular switch: Following activation by Ca 2ϩ -calmodulin, it can stay active for prolonged periods of time via autophosphorylation (6, 7). Reports that brief application of glutamate or NMDA to cultured hippocampal neurons induces CaMKII accumulation in spines (8-10) have created much interest because ␣CaMKII activation is both necessary and sufficient to induce synaptic plasticity (6, 11). It has been suggested that postsynaptic accumulation of ␣CaMKII could be responsible for the synapse-specificity of LTP, because it localizes the putative activated kinase close to its substrates, e.g., AMPA receptors (7, 12) and protects it from dephosphorylation (13). However, a crucial prediction of this hypothesis, namely that ␣CaMKII accumulates specifically and exclusively at synapses that undergo LTP, has never been tested experimentally.To address whether ␣CaMKII accumulates specifically in spines experiencing coincident activity, we developed an alloptical pairing protocol to induce synaptic plasticity at identified spines, combining two-photon uncaging of ...

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“…Confinement of CaMKII within spines arises from the geometry of the spine and through interactions with protein receptors and cytoskeletal elements within the postsynaptic density (PSD), which is the protein-rich region at the tip of the spine head. Global stimulation of NMDA receptors has previously been shown to result in the translocation of CaMKII from the dendritic shaft into spines (Strack et al 1997;Shen and Meyer 1999;Shen et al 2000;Bayer 2006). There are two main isoforms of CaMKII, known as CaMKIIα and CaMKIIβ.…”

Section: Introductionmentioning

confidence: 99%

Propagation of CaMKII translocation waves in heterogeneous spiny dendrites

Bressloff

2012

J. Math. Biol.

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CaMKII (Ca 2+ -calmodulin-dependent protein kinase II) is a key regulator of glutamatergic synapses and plays an essential role in many forms of synaptic plasticity. It has recently been observed experimentally that stimulating a local region of dendrite not only induces the local translocation of CaMKII from the dendritic shaft to synaptic targets within spines, but also initiates a wave of CaMKII translocation that spreads distally through the dendrite with an average speed of order 1µm/s. We have previously developed a simple reaction-diffusion model of CaMKII translocation waves that can account for the observed wavespeed and predicts wave propagation failure if the density of spines is too high. A major simplification of our previous model was to treat the distribution of spines as spatially uniform. However, there are at least two sources of heterogeneity in the spine distribution that occur on two different spatial scales. First, spines are discrete entities that are joined to a dendritic branch via a thin spine neck of submicron radius, resulting in spatial variations in spine density at the micron level. The second source of heterogeneity occurs on a much longer length scale and reflects the experimental observation that there is a slow proximal to distal variation in the density of spines. In this paper, we analyze how both sources of heterogeneity modulate the speed of CaMKII translocation waves along a spiny dendrite. We adapt methods from the study of the spread of biological invasions in heterogeneous environments, including homogenization theory of pulsating fronts and Hamilton-Jacobi dynamics of sharp interfaces.

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Transition from Reversible to Persistent Binding of CaMKII to Postsynaptic Sites and NR2B

Cited by 220 publications

References 60 publications

αCaMKII autophosphorylation levels differ depending on subcellular localization

αCaMKII autophosphorylation levels differ depending on subcellular localization

Optical induction of plasticity at single synapses reveals input-specific accumulation of αCaMKII

Propagation of CaMKII translocation waves in heterogeneous spiny dendrites

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