Protein kinase Mζ is necessary and sufficient for LTP maintenance

Ling, Douglas S.F.; Benardo, Larry S.; Serrano, Peter A.; Blace, Nancy; Kelly, M. J.; Crary, John F.

doi:10.1038/nn829

Cited by 394 publications

(498 citation statements)

References 15 publications

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“…It is an atypical PKC enzyme with the ability to be autonomously active once synthesized, thereby stabilizing lasting changes required for sustained LTP. [96][97][98][99] However more recent studies show that PKMz, is dispensable for LTP associated with memory. [100][101][102] In 1998, Tompa and Friedrich put forth the prion theory of memory wherein they suggested that propagation of a non-toxic conformational state of prions could underlie cellular functions like memory storage.…”

Section: Biochemical Models For Ltm Maintenancementioning

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: Biochemical Models For Ltm Maintenancementioning

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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“…Pharmacological experiments indicate that the atypical protein kinase C known as protein kinase Mζ (PKM-ζ) may be necessary and sufficient for the maintenance of L-LTP in the hippocampus (Ling et al, 2002;Pastalkova et al, 2006) and can also be involved in synaptic tagging . More recently, it has been proposed that CaMKII could also participate in setting synaptic tags for L-LTP capture, whereas MAPKs would play an equivalent role for L-LTD (Sajikumar et al, 2007a).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later

Barco

Armentia

Alarcón

2008

Neuroscience & Biobehavioral Reviews

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Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited ten years later, Neuroscience and Biobehavioral Reviews (2008Reviews ( ), doi:10.1016Reviews ( /j.neubiorev.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d m a n u s c r i p t A c c e p t e d m a n u s c r i p tThe STC hypothesis revisited 2 Abstract A decade ago, the synaptic tagging hypothesis was proposed to explain how newly synthesized plasticity products can be specifically targeted to active synapses. A growing number of studies have validated the seminal findings that gave rise to this model, as well as contributed to unveil and expand the range of mechanisms underlying late-associativity and neuronal computation.Here, we will review what it was learnt during this past decade regarding the cellular and molecular mechanisms underlying synaptic tagging and synaptic capture. The accumulated experimental evidence has widened the theoretical framework set by the synaptic tagging and capture (STC) model and introduced concepts that were originally considered part of alternative models for explaining synapse-specific LTP. As a result, we believe that the STC model, now improved and expanded with these new ideas and concepts, still represents the most compelling hypothesis to explain late-associativity in synapse-specific plasticity processes. We will also discuss the impact of this model in our view of the integrative capability of neurons and associative learning. wordsKeywords: synaptic plasticity; LTP; associative learning; neuronal computation; synaptic tagging; synaptic capture; metaplasticity A c c e p t e d m a n u s c r i p tThe STC hypothesis revisited 3 Contents

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“…In addition, during the protein synthesis-dependent, late form of LTP in the hippocampus, PKMz plays a role in the initial upregulation of new protein synthesis, including increased synthesis of PKMz itself, which is crucial for the transition from early-to late-LTP [11,12]. Following the de novo synthesis of PKMz [3], the autonomous activity of the kinase maintains synaptic potentiation for hours to days [8,9,13,14]. Similarly, after learning, the persistent activity of PKMz maintains many forms of long-term memory, including spatial [9] and trace conditioning [13] in the hippocampus and elementary associations [10,[15][16][17], extinction [18] and skilled sensorimotor memories [19] in the neocortex.…”

Section: Introductionmentioning

confidence: 99%

Cellular and subcellular localization of PKMζ

Hernández

Oxberry

Crary

et al. 2014

Phil. Trans. R. Soc. B

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In contrast to protein kinases that participate in long-term potentiation (LTP) induction and memory consolidation, the autonomously active atypical protein kinase C isoform, protein kinase Mzeta (PKMζ), functions in the core molecular mechanism of LTP maintenance and long-term memory storage. Here, using multiple complementary techniques for light and electron microscopic immunolocalization, we present the first detailed characterization of the cellular and subcellular distribution of PKMζ in rat hippocampus and neocortex. We find that PKMζ is widely expressed in forebrain with prominent immunostaining in hippocampal and neocortical grey matter, and weak label in white matter. In hippocampal and cortical pyramidal cells, PKMζ expression is predominantly somatodendritic, and electron microscopy highlights the kinase at postsynaptic densities and in clusters within spines. In addition, nuclear label and striking punctate immunopositive structures in a paranuclear and dendritic distribution are seen by confocal microscopy, occasionally at dendritic bifurcations. PKMζ immunoreactive granules are observed by electron microscopy in cell bodies and dendrites, including endoplasmic reticulum. The widespread distribution of PKMζ in nuclei, nucleoli and endoplasmic reticulum suggests potential roles of this kinase in cell-wide mechanisms involving gene expression, biogenesis of ribosomes and new protein synthesis. The localization of PKMζ within postsynaptic densities and spines suggests sites where the kinase stores information during LTP maintenance and long-term memory.

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Protein kinase Mζ is necessary and sufficient for LTP maintenance

Cited by 394 publications

References 15 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

Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later

Cellular and subcellular localization of PKMζ

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