Mechanisms of CaMKII action in long-term potentiation

Lisman, John; Yasuda, Ryohei; Raghavachari, Sridhar

doi:10.1038/nrn3192

Cited by 965 publications

(1,028 citation statements)

References 153 publications

(189 reference statements)

Supporting

Mentioning

995

Contrasting

Unclassified

Order By: Relevance

“…Constant exchange of subunits between the holoenzymes enable the spread of the active state between CaMKII enzyme assemblies. [76][77][78] These features allow the enzyme to be active even after the cessation of neuronal stimulation, a feature attributed to its role in long term memory storage.…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…BDNF also induces the translation of signaling proteins, as shown for CaMKIIa (Takei et al, 2004). The Ca 2þ -and calmodulindependent protein kinase II is a major constituent of the PSD and plays a structural role in enlarging and strengthening the synapse in the late phases of LTP (Lisman et al, 2012).…”

Section: Bdnf-induced Changes In the Neuronal Proteomementioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

View full text Add to dashboard Cite

a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

show abstract

“…[96][97][98] Activation of specific transmembrane channels increases the levels of Ca 2þ in the nucleus and the cytosol, including the cytosol's dendritic and axonal spaces. [99][100][101][102][103][104] Ca 2þ channels reside in the neuron's plasma membrane, particularly its synaptic regions, and also in intracellular membranes of the endoplasmic reticulum (ER), which is present in axons and dendrites as well. 96,97 The ER lumen is one site of Ca 2þ storage, in addition to extracellular space.…”

Section: The Fragment Generation Hypothesismentioning

confidence: 99%

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Varshavsky

2012

Protein Science

View full text Add to dashboard Cite

Despite extensive understanding of sleep regulation, the molecular-level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca 21 fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca 21 -activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca 21 transients) while fragment-destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness-increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol-induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca 21 alone or Ca 21 and its ionophore (Erickson et al., Science 1978;199:1219-1221 Harris, Pharmacol Biochem Behav 1979;10:527-534; Erickson et al., Pharmacol Biochem Behav 1980;12:651-656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.

show abstract

Mechanisms of CaMKII action in long-term potentiation

Cited by 965 publications

References 153 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

BDNF-induced local protein synthesis and synaptic plasticity

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Contact Info

Product

Resources

About