Activation of CaMKII in single dendritic spines during long-term potentiation

Lee, Seok-Jin R.; Escobedo-Lozoya, Yasmin; Szatmári, E; Yasuda, Ryohei

doi:10.1038/nature07842

Cited by 594 publications

(893 citation statements)

References 46 publications

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“…81 Following tetanic stimulation, CaMKII levels increase in the memory associated CA1 region of the brain and LTP induction stimulates CaMKII activity in single spines. 45,82 Several studies have shown that memory associated LTP is associated with CaMKII activation and phosphorylation. Consistently inhibitors of CaMKII and mutation in the T286 residue blocks specifically the induction of LTP.…”

Section: Rna Regulation Is Central To Long-term Memory Formationmentioning

confidence: 99%

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Sudhakaran

Ramaswami

2016

RNA Biology

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Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs function in synapse specific plasticity underlying LTM.

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Section: Rna Regulation Is Central To Long-term Memory Formationmentioning

confidence: 99%

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Sudhakaran

Ramaswami

2016

RNA Biology

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“…CaMKII is multifunctional and plays important roles in synaptic transmission and plasticity that affect behavior, learning, and memory. At molecular level, it modulates a wide range of cellular processes including calcium (Ca 2+ ) homeostasis, gene transcription, receptor function, and cytoskeletal alterations [1,[4][5][6][7][8][9]. It has been implicated in both neuronal death and survival, and its precise role in brain ischemia remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway

Das

Roy

et al. 2018

Mol Neurobiol

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Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) has long been implicated in neuronal injury caused by acute ischemia/ reperfusion (I/R). However, its precise role and regulatory mechanisms remain obscure. Here, we investigated the role of the CaMKII family in neuronal survival during I/R. Our data indicated that CAMK2D/CaMKIIδ and CAMK2G/CaMKIIγ were selectively upregulated in a time-dependent manner at both transcriptional and protein levels after acute ischemia. Overexpression of CaMKIIδ promoted neuronal survival, while their depletion exacerbated ischemic neuronal death. Similar to CaMKIIδ, knockdown of CAMKIIγ resulted in significant neuronal death after I/R. We further identified CaMKIIδ 2 as the subtype that is selectively induced by I/R in primary neurons. The induction of CaMKIIδ was controlled in part by a pair of long non-coding RNAs (lncRNAs), C2dat1 and C2dat2. C2dat2, similar to C2dat1, was upregulated by I/R and cooperated with C2dat1 to modulate CaMKIIδ expression. Knockdown of C2dat1/2 blocked OGD/R-induced CaMKIIδ expression and decreased neuronal survival but did not affect the levels of CaMKIIγ, indicating specific targeting of CAMK2D by C2dat1/2. Mechanistically, I/R-induced CaMKIIδ and CaMKIIγ caused the upregulation of IKKα/β and further activation of the NF-κB signaling pathway to protect neurons from ischemic damage. Genetically, downregulating p65 subunit of NF-κB in mice increased I/R-induced neuronal death by blocking the activity of CaMKII/IKK/IκBα/NF-κB signaling axis. In summary, CaMKIIδ and CaMKIIγ are novel I/R-induced genes that promote neuronal survival during ischemic injury. The upregulation of these CaMKII kinases led to activation of the NF-κB signaling pathway, which protects neurons from ischemic damage.

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“…The upregulation of AMPA receptor numbers in synapses is a well-established mechanism for the expression of long-term potentiation (LTP) (Malenka and Bear 2004). On the other hand, it has also been found that inducing LTP at a single synapse activates CaMKII within the spine containing the synapse but neither induces LTP at nearby synapses nor raises CaM-KII content in nearby spines (Zhang et al 2008;Lee et al 2009). This is consistent with our previous result that there exists an activation threshold for wave propagation, which in the case of a homogeneous spine distribution is k = h. As we have shown in this paper, spine clustering reduces this threshold.…”

Section: Discussionmentioning

confidence: 99%

“…First, CaMKII is found to be abundant at postsynaptic sites where it can detect changes in the local levels of Ca 2+ entering the synapse following plasticity-inducing stimuli, via binding of CaMKII to Ca 2+ /CaM. Activated CaMKII then phosphorylates substrates responsible for the expression of synaptic plasticity, namely, the number and the conductivity of synaptic AMPA receptors (Fukunaga et al 1995;Mammen et al 1997;Barria et al 1997a;Derkach et al 1999;Lee et al 2009). Second, once activated, CaMKII can transition into a Ca 2+ /CaM-independent, hyper-activated state via the autophosphorylation of neighboring enzymatic subunits (Hanson et al 1994; Rich and Schulman 1998), and thus continue to phosphorylate its substrates even after the plasticity-inducing Ca 2+ signal has ended (Saitoh and Schwartz 1985;Miller and Kenney 1986;Lou et al 1986;Yang and Schulman 1999).…”

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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Activation of CaMKII in single dendritic spines during long-term potentiation

Cited by 594 publications

References 46 publications

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Ischemic Injury-Induced CaMKIIδ and CaMKIIγ Confer Neuroprotection Through the NF-κB Signaling Pathway

Propagation of CaMKII translocation waves in heterogeneous spiny dendrites

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