title: Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage.
abstract: The cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a regulator of local protein synthesis, is the mouse homolog of ApCPEB, a functional prion protein in Aplysia. Here, we provide evidence that CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase. In hippocampal cultures, CPEB3 activated by Neuralized1-mediated ubiquitination leads both to the growth of new dendritic spines and to an increase of the GluA1 and GluA2 subunits of AMPA receptors, two CPEB3 targets essential for synaptic plasticity. Conditional overexpression of Neuralized1 similarly increases GluA1 and GluA2 and the number of spines and functional synapses in the hippocampus and is reflected in enhanced hippocampal-dependent memory and synaptic plasticity. By contrast, inhibition of Neuralized1 reduces GluA1 and GluA2 levels and impairs hippocampal-dependent memory and synaptic plasticity. These results suggest a model whereby Neuralized1-dependent ubiquitination facilitates hippocampal plasticity and hippocampal-dependent memory storage by modulating the activity of CPEB3 and CPEB3-dependent protein synthesis and synapse formation.
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Pavlopoulos
authors.forename: Pierre
authors.initials: P
authors.lastname: Trifilieff
authors.forename: Vivien
authors.initials: V
authors.lastname: Chevaleyre
authors.forename: Luana
authors.initials: L
authors.lastname: Fioriti
authors.forename: Sakellarios
authors.initials: S
authors.lastname: Zairis
authors.forename: Andrew
authors.initials: A
authors.lastname: Pagano
authors.forename: Gaël
authors.initials: G
authors.lastname: Malleret
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D006624:Hippocampus / Q000378:metabolism; D008568:Memory; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity; D011061:Poly A / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013569:Synapses
chemical_list: D020413:3' Untranslated Regions; D009419:Nerve Tissue Proteins; D011061:Poly A; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C477603:Cpeb3 protein, mouse; C438900:Neurl protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2