Neuralized1 Activates CPEB3: A Function for Nonproteolytic Ubiquitin in Synaptic Plasticity and Memory Storage

Pavlopoulos, Elias; Trifilieff, Pierre; Chevaleyre, Vivien; Fioriti, Luana; Zairis, Sakellarios; Pagano, Andrew; Malleret, Gaël; Kandel, Eric R.

doi:10.1016/j.cell.2011.09.056

Cited by 174 publications

(208 citation statements)

References 60 publications

(62 reference statements)

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“…These findings suggest a model whereby SUMO regulates translation of mRNAs and synaptic plasticity by modulating the aggregation of CPEB3 Because SUMOylation keeps it in an inactive state, what activates CPEB3? Pavlopoulos et al found that CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase (Pavlopoulos et al 2011). CPEB3 interacts with Neuralized1 in dendrites of adult hippocampal neurons.…”

Section: Prion-like Proteins and Memorymentioning

confidence: 99%

The Role of Functional Prion-Like Proteins in the Persistence of Memory

Kandel

2016

Cold Spring Harb Perspect Biol

101

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Section: Prion-like Proteins and Memorymentioning

confidence: 99%

The Role of Functional Prion-Like Proteins in the Persistence of Memory

Kandel

2016

Cold Spring Harb Perspect Biol

101

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“…Neuralized overexpression leads to structural plasticity of dendritic spines and upregulation of AMPA receptors GluA1 and GluA2 that are regulatory targets of CPEB3. 157 Like CPEB1 and Orb2 in Drosophila, CPEB3 forms aggregates, which are selfpropagating and heritable in yeast, in a N terminal subdomain dependent manner. CPEB3 aggregation is reported to occur in mouse brain upon appropriate neuronal stimulation.…”

Section: Mouse Cpebmentioning

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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“…In the nervous system, the UPS regulates several aspects of synaptic function, such as spinogenesis (Hamilton et al, 2012), presynaptic neurotransmission (Willeumier et al, 2006;Jiang et al, 2010), long-term potentiation (Dong et al, 2008;Cajigas et al, 2010;Pavlopoulos et al, 2011), synaptic scaling , apical dendrite outgrowth/ polarization (Hamilton and Zito, 2013;Miao et al, 2013;Vadhvani et al, 2013), dendritic arborization (Puram et al, 2013), axon growth (Yang et al, 2013), and synapse formation and elimination (Yi and Ehlers, 2007).…”

Section: Role Of Ups In Nervous Systemmentioning

confidence: 99%

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Caldeira

Salazar

Curcio

et al. 2014

Progress in Neurobiology

110

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A B S T R A C TThe ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitincontaining proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. ß

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Neuralized1 Activates CPEB3: A Function for Nonproteolytic Ubiquitin in Synaptic Plasticity and Memory Storage

Cited by 174 publications

References 60 publications

The Role of Functional Prion-Like Proteins in the Persistence of Memory

The Role of Functional Prion-Like Proteins in the Persistence of Memory

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

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

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