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

Si, Kausik; Kandel, Eric R.

doi:10.1101/cshperspect.a021774

Cited by 105 publications

(91 citation statements)

References 63 publications

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“…In searching for such a translational regulator that could help explain the phenomenon of synaptic tagging and capture, Si and Kandel (2016) focused on CPEB, a protein that Joel Richter found to activate dormant mRNAs in other biological contexts (McGrew et al 1989;Si et al 2003a,b). Earlier work on Xenopus oocytes revealed that some translationally dormant mRNAs are activated following elongation of their poly(A) tail (McGrew et al 1989;Stebbins-Boaz et al 1996;Schroeder et al 1999).…”

Section: Identification and Characterization Of Aplysia Cpebmentioning

confidence: 99%

“…Si and Kandel (2016) postulated that the conversion of ApCPEB to the multimeric state should be regulated by synaptic activity. To address this question, Si et al (2010) expressed enhanced green fluorescent protein (EGFP)-tagged ApCPEB in the sensory-to-motor neuron coculture, waited 48 h for the expression to reach a steady-state level, and then stimulated the cells with five pulses of 5-HT, the neuromodulatory transmitter released during behavioral learning.…”

Section: Aggregation Of Aplysia Cpeb Is Induced By 5-htmentioning

confidence: 99%

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Functional Prions in the Brain

Rayman

Kandel

2016

Cold Spring Harb Perspect Biol

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Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.

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Section: Identification and Characterization Of Aplysia Cpebmentioning

confidence: 99%

Section: Aggregation Of Aplysia Cpeb Is Induced By 5-htmentioning

confidence: 99%

Functional Prions in the Brain

Rayman

Kandel

2016

Cold Spring Harb Perspect Biol

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“…That being stated, it is useful to outline key requirements for establishing a model, in order to have an objective yardstick for assessing the conclusiveness of current data, which have been discussed and/ or reviewed in recent articles. 9,10 (a) Synaptic activity that triggers long-term memory should be demonstrated to result in conformational switch of CPEB from a monomeric to oligomeric prion-like form at active but not at inactive synapses. (b) At the activated synapse, the new oligomeric CPEB should be capable of self-renewal, recruiting monomeric CPEB into oligomers over the extended period for which memory is retained.…”

Section: Characterization Of Prions and Prion Domainsmentioning

confidence: 99%

“…Such a model has been proposed and is supported by several observations of the prion-domain containing RNA regulatory protein CPEB. 9,10 This review will introduce diverse aspects of molecular biology of long-term memory, discuss the role of translational control mechanisms in long-term synaptic plasticity with a particular focus on the role and potential mechanisms by which prion-domain containing RNA-binding proteins enable longterm memory formation and retention.…”

Section: Introductionmentioning

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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“…Prion like proteins are critical for maintaining long term memory in mice [8] and the role of prions connected to memory is described [9]. They appear to be involved in the storage of information in the neurons of all animal species.…”

Section: The Storage Of Information In the Neuronsmentioning

confidence: 99%

Alzheimer's Disease: What is the Connection between Amyloid Plaques, Magnetite and Memory?

Størmer¹

2017

J Alzheimers Dis Parkinsonism

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

Cited by 105 publications

References 63 publications

Functional Prions in the Brain

Functional Prions in the Brain

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

Alzheimer's Disease: What is the Connection between Amyloid Plaques, Magnetite and Memory?

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