Synaptic memory requires CaMKII

Tao, Wucheng; Lee, Joel; Chen, Xiumin; Díaz-Alonso, Javier; Zhou, Jing; D, Samuel Pleasure M

doi:10.7554/elife.60360

Cited by 48 publications

(55 citation statements)

References 98 publications

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“…The importance of CaMKII activity, and its idiosyncratic subunit arrangement in dodecameric holoenzymes, have stimulated great interest in its mechanisms of action. Particularly beguiling is the idea that CaMKII can convert brief Ca 2+ signals corresponding to decisions, calculations and comparisons in neurons into sustained phosphorylation of targets in order to store information in neural circuits (Lisman, Schulman and Cline, 2002; Coultrap and Bayer, 2012; Tao et al ., 2021). The prevailing model for the requisite spatial and temporal spread of CaMKII autonomous activity argues that CaMKII must exchange subunits between activated and naïve (unactivated) holoenzymes (Stratton et al ., 2014; Bhattacharyya et al ., 2016), principally because previous work suggests autophosphorylation between holoenzymes does not occur (Miller, S. G. & Kennedy, 1986; Hanson et al ., 1994; Rich and Schulman, 1998).…”

Section: Discussionmentioning

confidence: 99%

CaMKII activity spreads by inter-holoenzyme phosphorylation

Lučić¹,

Héluin²,

Jiang³

et al. 2022

Preprint

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The dodecameric protein kinase CaMKII is expressed throughout the body. The alpha isoform is responsible for synaptic plasticity and participates in memory through its phosphorylation of synaptic proteins. Its elaborate subunit organization and propensity for autophosphorylation allow it to preserve neuronal plasticity across space and time. The prevailing hypothesis for the spread of CaMKII activity, involving shuffling of subunits between activated and naive holoenzymes, is broadly termed subunit exchange. In contrast to the expectations of previous work, we found little evidence for subunit exchange upon activation, and no effect of restraining subunits to their parent holoenzymes. Rather, mass photometry, crosslinking mass spectrometry, single molecule TIRF microscopy and biochemical assays identify inter-holoenzyme phosphorylation (IHP) as the mechanism for spreading phosphorylation. The transient, activity-dependent formation of groups of holoenzymes is well suited to the speed of neuronal activity. Our results place fundamental limits on the activation mechanism of this kinase.

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Section: Discussionmentioning

confidence: 99%

CaMKII activity spreads by inter-holoenzyme phosphorylation

Lučić¹,

Héluin²,

Jiang³

et al. 2022

Preprint

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“…Therefore, CaMKII is a key protein kinase involved in neural plasticity and memory formation [ 79 , 80 , 81 , 82 ]. Experimental blocking of CaMKII inhibits synaptic transmission [ 83 ]. Accordingly, in our studies, we observed a decrease in the expression level of the CaMKII gene predominantly in the strains with double deletions and strains with CBS deletion.…”

Section: Discussionmentioning

confidence: 99%

Genes Responsible for H2S Production and Metabolism Are Involved in Learning and Memory in Drosophila melanogaster

et al. 2022

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The gasotransmitter hydrogen sulfide (H2S) produced by the transsulfuration pathway (TSP) is an important biological mediator, involved in many physiological and pathological processes in multiple higher organisms, including humans. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) enzymes play a central role in H2S production and metabolism. Here, we investigated the role of H2S in learning and memory processes by exploring several Drosophila melanogaster strains with single and double deletions of CBS and CSE developed by the CRISPR/Cas9 technique. We monitored the learning and memory parameters of these strains using the mating rejection courtship paradigm and demonstrated that the deletion of the CBS gene, which is expressed predominantly in the central nervous system, and double deletions completely block short- and long-term memory formation in fruit flies. On the other hand, the flies with CSE deletion preserve short- and long-term memory but fail to exhibit long-term memory retention. Transcriptome profiling of the heads of the males from the strains with deletions in Gene Ontology terms revealed a strong down-regulation of many genes involved in learning and memory, reproductive behavior, cognition, and the oxidation–reduction process in all strains with CBS deletion, indicating an important role of the hydrogen sulfide production in these vital processes.

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“…Over three decades of study suggests that CaMKII is one of the key players in LTP ( Zalcman et al, 2018 ). Inhibition of CaMKII activity blocks the induction as well as maintenance of LTP ( Malenka et al, 1989 ; Malinow et al, 1989 ; Tao et al, 2021 ). In response to sufficient influx of Ca 2+ into the postsynaptic neuron, CaMKII gets activated by the binding of Ca 2+ /CaM and autophosphorylated at Thr 286 .…”

Section: Ca 2+ /Calmodulin-dependent Protein Kinas...mentioning

confidence: 99%

“…While considerable insights have been obtained on the mechanisms by which LTP-inducing tetanic stimuli are converted to enhanced AMPAR activity at the postsynaptic side, the mechanisms by which the potentiated state is maintained has been intensively debated ( Giese et al, 1998 ; Buard et al, 2010 ; Coultrap et al, 2012 ; Chang et al, 2017 ; Giese, 2021 ; Tao et al, 2021 ). Even long-lasting structural changes such as spine enlargement are maintained by dynamic molecular mechanisms ( Gamache et al, 2020 ).…”

Section: Ca 2+ /Calmodulin-dependent Protein Kinas...mentioning

confidence: 99%

“…These studies suggest that Thr 286 autophosphorylation might have a major role in the initial capture of information encoded in the synaptic Ca 2+ spikes with more efficiency. However, inhibition of CaMKII activity can erase LTP showing the involvement of CaMKII in LTP maintenance, further suggesting that CaMKII acts as a molecular storage device ( Tao et al, 2021 ).…”

Section: Ca 2+ /Calmodulin-dependent Protein Kinas...mentioning

confidence: 99%

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Role of Ca2+/Calmodulin-Dependent Protein Kinase Type II in Mediating Function and Dysfunction at Glutamatergic Synapses

Mohanan

Gunasekaran

Jacob

et al. 2022

Front. Mol. Neurosci.

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Glutamatergic synapses harbor abundant amounts of the multifunctional Ca2+/calmodulin-dependent protein kinase type II (CaMKII). Both in the postsynaptic density as well as in the cytosolic compartment of postsynaptic terminals, CaMKII plays major roles. In addition to its Ca2+-stimulated kinase activity, it can also bind to a variety of membrane proteins at the synapse and thus exert spatially restricted activity. The abundance of CaMKII in glutamatergic synapse is akin to scaffolding proteins although its prominent function still appears to be that of a kinase. The multimeric structure of CaMKII also confers several functional capabilities on the enzyme. The versatility of the enzyme has prompted hypotheses proposing several roles for the enzyme such as Ca2+ signal transduction, memory molecule function and scaffolding. The article will review the multiple roles played by CaMKII in glutamatergic synapses and how they are affected in disease conditions.

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Synaptic memory requires CaMKII

Cited by 48 publications

References 98 publications

CaMKII activity spreads by inter-holoenzyme phosphorylation

CaMKII activity spreads by inter-holoenzyme phosphorylation

Genes Responsible for H2S Production and Metabolism Are Involved in Learning and Memory in Drosophila melanogaster

Role of Ca2+/Calmodulin-Dependent Protein Kinase Type II in Mediating Function and Dysfunction at Glutamatergic Synapses

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