The Experts below are selected from a list of 2106 Experts worldwide ranked by ideXlab platform
Joel D. Richter - One of the best experts on this subject based on the ideXlab platform.
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Research Selective Modulation of Some Forms of Schaffer Collateral-CA1 Synaptic Plasticity in Mice With a Disruption of the CPEB-1 Gene
2016Co-Authors: Juan M Alarcon, Martin Theis, Rebecca Hodgman, Yishuian Huang, Eric R. K, Joel D. RichterAbstract:CPEB-1 is a sequence-specific RNA binding protein that stimulates the polyadenylation-induced translation of mRNAs containing the cytoplasmic polyadenylation element (CPE). Although CPEB-1 was identified originally in Xenopus oocytes, it has also been found at postsynaptic sites of hippocampal neurons where, in response to N-methyl-D-aspartate receptor activation, it is thought to induce the polyadenylation and translation of CaMKII and perhaps other CPE-containing mRNAs. Because some forms of synaptic modification appear to be influenced by local (synaptic) protein synthesis, we examined long-term potentiation (LTP) in CPEB-1 knockout mice. Although the basal synaptic transmission of Schaffer collateral-CA1 neurons was not affected in the knockout mice, we found that there was a modest deficit in LTP evoked by a single train of 100 Hz stimulation, but a greater deficit in LTP evoked by one train of theta-burst stimulation. In contrast, LTP evoked by either four trains of 100 Hz stimulation or five trains of theta-burst stimulation were not or were only modestly affected, respectively. The deficit in LTP evoked by single stimulation in knockout mice appeared several minutes after tetanic stimulation. Long-term depression (LTD) evoked by 1 Hz stimulation was moderately facilitated; however, a stronger and more enduring form of LTD induced by paired-pulse 1 Hz stimulation was unaffected. These data suggest that CPEB-1 contributes in the translational control of mRNAs that is critical only for some selected forms of LTP and LTD. Recent studies indicate that local protein synthesis can contrib
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Brief Communication Reduced extinction of hippocampal-dependent memories in CPEB knockout mice
2016Co-Authors: Joanne Berger-sweeney, Ruth N Zearfoss, Joel D. RichterAbstract:CPEB is a sequence-specific RNA binding protein that regulates translation at synapses. In neurons of CPEB knockout mice, synaptic efficacy is reduced. Here, we have performed a battery of behavioral tests and find that relative to wild-type animals, CPEB knockout mice, although similar on many baseline behaviors, have reduced extinction of memories on two hippocampal-dependent tasks. A corresponding microarray analysis reveals that about 0.14 % of hippocampal genes have an altered expression in the CPEB knockout mouse. These data suggest that CPEB-dependent local protein synthesis may be an important cellular mechanism underlying extinction of hippocampal-dependent memories. The modulation of synaptic strength, which underlies long-term memory storage (Hering and Sheng 2001), may involve “synaptic tagging, ” where a stimulated synapse is tagged with a molecular mark that a neuron uses to distinguish naive from stimulated synapses (Martin et al. 2000). Based on the recognition of this tag, a neuron can modify the strength of its synaptic response upon subsequent stimulation. While the nature of the tag is un-known, protein synthesis is involved in its establishment or rec
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Cytoplasmic Polyadenylation Element Binding Proteins in Development, Health, and Disease
Annual review of cell and developmental biology, 2014Co-Authors: Maria Ivshina, Paul Lasko, Joel D. RichterAbstract:The cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific mRNA binding proteins that control translation in development, health, and disease. CPEB1, the founding member of this family, has become an important model for illustrating general principles of translational control by cytoplasmic polyadenylation in gametogenesis, cancer etiology, synaptic plasticity, learning, and memory. Although the biological functions of the other members of this protein family in vertebrates are just beginning to emerge, it is already evident that they, too, mediate important processes, such as cancer etiology and higher cognitive function. In Drosophila, the CPEB proteins Orb and Orb2 play key roles in oogenesis and in neuronal function, as do related proteins in Caenorhabditis elegans and Aplysia. We review the biochemical features of the CPEB proteins, discuss their activities in several biological systems, and illustrate how understanding CPEB activity in model organisms has an important impa...
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bidirectional control of mrna translation and synaptic plasticity by the cytoplasmic polyadenylation complex
Molecular Cell, 2012Co-Authors: Tsuyoshi Udagawa, Sharon A Swanger, Gary J Bassell, Koichi Takeuchi, Jong Heon Kim, Vijayalaxmi C Nalavadi, Jihae Shin, Lori J Lorenz, Suzanne R Zukin, Joel D. RichterAbstract:Translational control of mRNAs in dendrites is essential for certain forms of synaptic plasticity and learning and memory. CPEB is an RNA-binding protein that regulates local translation in dendrites. Here, we identify poly(A) polymerase Gld2, deadenylase PARN, and translation inhibitory factor neuroguidin (Ngd) as components of a dendritic CPEB-associated polyadenylation apparatus. Synaptic stimulation induces phosphorylation of CPEB, PARN expulsion from the ribonucleoprotein complex, and polyadenylation in dendrites. A screen for mRNAs whose polyadenylation is altered by Gld2 depletion identified >100 transcripts including one encoding NR2A, an NMDA receptor subunit. shRNA depletion studies demonstrate that Gld2 promotes and Ngd inhibits dendritic NR2A expression. Finally, shRNA-mediated depletion of Gld2 in vivo attenuates protein synthesis-dependent long-term potentiation (LTP) at hippocampal dentate gyrus synapses; conversely, Ngd depletion enhances LTP. These results identify a pivotal role for polyadenylation and the opposing effects of Gld2 and Ngd in hippocampal synaptic plasticity.
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CPEB mediated zo 1 mrna localization is required for epithelial tight junction assembly and cell polarity
Nature Communications, 2012Co-Authors: Kentaro Nagaoka, Tsuyoshi Udagawa, Joel D. RichterAbstract:CPEB is a translational regulatory sequence-specific RNA-binding protein that controls germ cell development. Here we show that CPEB heterozygous female mice are fertile but contain disorganized mammary epithelial cells, in which zonal occludens-1 and claudin-3, apical tight-junction proteins, are mislocalized. CPEB depletion from mammary epithelial cells disrupts zonal occludens-1 apical localization and tight-junction distribution; conversely, ectopic expression of CPEB enhances zonal occludens-1 localization. CPEB and zonal occludens-1 mRNA are co-localized apically and zonal occludens-1 3' untranslated region-binding sites for CPEB are necessary for RNA localization. In a three-dimensional culture system that models lumen-containing mammary ducts, depletion of CPEB or zonal occludens-1 impairs central cavity formation, indicating a loss of cell polarity. Cavity formation in zonal occludens-1-depleted cells is rescued when they are transduced with zonal occludens-1 mRNA containing, but not lacking, CPEB-binding sites. Our data demonstrate that CPEB-mediated zonal occludens-1 mRNA localization is essential for tight-junction assembly and mammary epithelial cell polarity.
Eric R. Kandel - One of the best experts on this subject based on the ideXlab platform.
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Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
Frontiers in cellular neuroscience, 2020Co-Authors: Bettina Drisaldi, Eric R. Kandel, Luca Colnaghi, Amir Levine, Yan-you Huang, Anna M. Snyder, Daniel J. Metzger, Martin Theis, Denise B. Kandel, Luana FioritiAbstract:A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored. Little is known about any of the mechanisms for maintaining memories for addictive behavior. To address the mechanisms whereby addictive behavior is maintained over time, we utilized a conditional transgenic mouse model expressing a dominant-negative version of CPEB1 that abolishes the activity in the forebrain of two of the four CPEB isoforms (CPEB1 and CPEB3). We found that, following cocaine administration, these dominant-negative (DN) CPEB mice showed a significant decrease, when compared to wild type (WT) mice, in both locomotor sensitizations and conditioned place preference (CPP), two indices of addictive behavior. Supporting these behavioral results, we also found a difference between WT and DN-CPEB1-3 mice in the cocaine-induced synaptic depression in the core of the Nucleus Accumbens (NAc). Finally, we found that (1) CPEB is reduced in transgenic mice following cocaine injections and that (2) FosB, known for its contribution to establishing the addictive phenotype, when its expression in the striatum is increased by drug administration, is a novel target of CPEBs molecules. Thus, our study highlights how CPEB1 and CPEB3 act on target mRNAs to build the neuroadaptative implicit memory responses that lead to the development of the cocaine addictive phenotypes in mammals.
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microrna 22 gates long term heterosynaptic plasticity in aplysia through presynaptic regulation of CPEB and downstream targets
Cell Reports, 2015Co-Authors: Ferdinando Fiumara, Priyamvada Rajasethupathy, Igor Antonov, Stylianos Kosmidis, Wayne S Sossin, Eric R. KandelAbstract:The maintenance phase of memory-related long-term facilitation (LTF) of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT)-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22) that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC), another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity.
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characterization of prion like conformational changes of the neuronal isoform of aplysia CPEB
Nature Structural & Molecular Biology, 2013Co-Authors: Ansgar B Siemer, Bindu L Raveendra, Sathyanarayanan V Puthanveettil, Wayne A Hendrickson, Eric R. KandelAbstract:The protein CPEB, required for learning-related synaptic plasticity in the snail Aplysia, has been suggested to convert from a soluble to a prion-like state. Now these conformational forms of Aplysia CPEB are directly observed, with the prion form showing enhanced binding to target mRNAs.
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the molecular biology of memory camp pka cre creb 1 creb 2 and CPEB
Molecular Brain, 2012Co-Authors: Eric R. KandelAbstract:The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all over the world. These are six key steps in the molecular biological delineation of short-term memory and its conversion to long-term memory for both implicit (procedural) and explicit (declarative) memory. I here first trace the background for the clinical and behavioral studies of implicit memory that made a molecular biology of memory storage possible, and then detail the discovery and early history of these six molecular steps and their roles in explicit memory.
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a molecular circuit composed of CPEB 1 and c jun controls growth hormone mediated synaptic plasticity in the mouse hippocampus
The Journal of Neuroscience, 2008Co-Authors: Ruth N Zearfoss, Eric R. Kandel, Juan Marcos Alarcon, Pierre Trifilieff, Joel D. RichterAbstract:Cytoplasmic polyadenylation element binding protein 1 (CPEB-1) resides at postsynaptic sites in hippocampal neurons in which it controls polyadenylation-induced translation. CPEB-1 knock-out (KO) mice display defects in some forms of synaptic plasticity and hippocampal-dependent memories. To identify CPEB-1-regulated mRNAs, we used proteomics to compare polypeptides in wild-type (WT) and CPEB-1 KO hippocampus. Growth hormone (GH) was reduced in the KO hippocampus, as were the GH signaling molecules phospho-JAK2 and phospho-STAT3. GH mRNA and pre-mRNA were reduced in the KO hippocampus, suggesting that CPEB-1 controls GH transcription. The transcription factor c-Jun, which binds the GH promoter, was also reduced in the KO hippocampus, as was its ability to coimmunoprecipitate chromatin containing the GH promoter. CPEB-1 binds c-Jun 3′ untranslated region CPEs in vitro and coimmunoprecipitates c-Jun RNA in vivo. GH induces long-term potentiation (LTP) when applied to hippocampal slices from WT and CPEB-1 KO mice, but the magnitude of LTP induced by GH in KO mice is reduced. Pretreatment with GH did not reverse the LTP deficit observed in KO mice after theta-burst stimulation (TBS). Cordycepin, an inhibitor of polyadenylation, disrupted LTP induced by either GH application or TBS. Finally, GH application to hippocampal slices induced JAK2 phosphorylation in WT but not KO animals. These results indicate that CPEB-1 control of c-Jun mRNA translation regulates GH gene expression and resulting downstream signaling events (e.g., synaptic plasticity) in the mouse hippocampus.
Maurizio Giustetto - One of the best experts on this subject based on the ideXlab platform.
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a neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse specific long term facilitation in aplysia
Cell, 2003Co-Authors: Maurizio Giustetto, Ami Etki, Ruby Hsu, Agnieszka M Janisiewicz, Maria Conchetta Miniaci, Jounghu Kim, Huixiang Zhu, Eric R. KandelAbstract:Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark.
Agnieszka M Janisiewicz - One of the best experts on this subject based on the ideXlab platform.
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A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia
'Elsevier BV', 2019Co-Authors: Si K, Agnieszka M Janisiewicz, Maria Conchetta Miniaci, Giustetto M, Etkin A, Hsu R, Jh Kim, Hx ZhuAbstract:Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark.X11283sciescopu
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a neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse specific long term facilitation in aplysia
Cell, 2003Co-Authors: Maurizio Giustetto, Ami Etki, Ruby Hsu, Agnieszka M Janisiewicz, Maria Conchetta Miniaci, Jounghu Kim, Huixiang Zhu, Eric R. KandelAbstract:Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark.
Maria Conchetta Miniaci - One of the best experts on this subject based on the ideXlab platform.
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A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia
'Elsevier BV', 2019Co-Authors: Si K, Agnieszka M Janisiewicz, Maria Conchetta Miniaci, Giustetto M, Etkin A, Hsu R, Jh Kim, Hx ZhuAbstract:Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark.X11283sciescopu
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a neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse specific long term facilitation in aplysia
Cell, 2003Co-Authors: Maurizio Giustetto, Ami Etki, Ruby Hsu, Agnieszka M Janisiewicz, Maria Conchetta Miniaci, Jounghu Kim, Huixiang Zhu, Eric R. KandelAbstract:Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark.
