The Neuralized-1 ubiquitin ligase regulates CPEB3-dependent protein synthesis of AMPA receptors in adult mammalian neurons and enhances synaptic plasticity and memory

Abstract

Event Abstract Back to Event The Neuralized-1 ubiquitin ligase regulates CPEB3-dependent protein synthesis of AMPA receptors in adult mammalian neurons and enhances synaptic plasticity and memory Elias Pavlopoulos1*, Pierre Trifilieff1, Vivien Chevaleyre1, Sakellarios Zairis1, Gael Malleret2, Steven Soegelbaum1 and Eric Kandel1 1 Columbia University, United States 2 Universite Clasite Claude Bernard Lyon1, France Recent studies in Drosophila have delineated the Neuralized ubiquitin ligase as limiting for long-term memory formation. We now ask does this ligase have a similar role in hippocampal based memory storage in mice? We find that the mouse homologue of Drosophila neur gene, Neurl1, is present in the forebrain of the adult mouse, and is expressed at particularly high levels in the hippocampus. Neurl1 protein is predominantly localized in dendrites at post-synaptic sites and its level is increased by synaptic activity. To investigate the role of Neurl1 in memory, we generated mice that conditionally over-express Neurl1 in the forebrain and in particular with high levels of expression in the hippocampus. In these mice we find that over-expression of Neurl1 in the hippocampus significantly enhances hippocampal-dependent memory, as well as long-term potentiation in the Schaeffer-collateral pathway of acute adult hippocampal slices. This indicates that it is also a limiting factor for memory processes in mammals. In investigating how Neurl1 acts to enhance memory, we found that over-expression of Neurl1 results in increased number of functional synapses in the hippocampus as well as an overall increase in GluR1 and GluR2 subunits of AMPA receptors (AMPARs), both essential components in synaptic plasticity and memory. This increase in GluR1 and GluR2 was independent of transcription or recycling, suggesting a role of Neurl1 in the regulation of their translation. Indeed, we find that the GluR1 and GluR2 mRNAs are targets of and are controlled by a regulator of protein synthesis, the cytoplasmic polyadenylation element-binding protein 3 (CPEB3). Neurl1 over-expression results both in increased levels of CPEB3 and in up-regulation of CPEB3-dependent translation of AMPARs. These results suggest a model whereby Neuralized-1 facilitates hippocampal plasticity and hippocampal-dependent memory by modulating the levels of CPEB3 and of CPEB3-dependent synthesis of GluR1 and GluR2. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Pavlopoulos E, Trifilieff P, Chevaleyre V, Zairis S, Malleret G, Soegelbaum S and Kandel E (2009). The Neuralized-1 ubiquitin ligase regulates CPEB3-dependent protein synthesis of AMPA receptors in adult mammalian neurons and enhances synaptic plasticity and memory. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.256 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2009; Published Online: 12 Jun 2009. * Correspondence: Elias Pavlopoulos, Columbia University, New York, United States, ep2185@columbia.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elias Pavlopoulos Pierre Trifilieff Vivien Chevaleyre Sakellarios Zairis Gael Malleret Steven Soegelbaum Eric Kandel Google Elias Pavlopoulos Pierre Trifilieff Vivien Chevaleyre Sakellarios Zairis Gael Malleret Steven Soegelbaum Eric Kandel Google Scholar Elias Pavlopoulos Pierre Trifilieff Vivien Chevaleyre Sakellarios Zairis Gael Malleret Steven Soegelbaum Eric Kandel PubMed Elias Pavlopoulos Pierre Trifilieff Vivien Chevaleyre Sakellarios Zairis Gael Malleret Steven Soegelbaum Eric Kandel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.