title: The CPEB3 Protein Is a Functional Prion that Interacts with the Actin Cytoskeleton.
abstract: The mouse cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a translational regulator implicated in long-term memory maintenance. Invertebrate orthologs of CPEB3 in Aplysia and Drosophila are functional prions that are physiologically active in the aggregated state. To determine if this principle applies to the mammalian CPEB3, we expressed it in yeast and found that it forms heritable aggregates that are the hallmark of known prions. In addition, we confirm in the mouse the importance of CPEB3's prion formation for CPEB3 function. Interestingly, deletion analysis of the CPEB3 prion domain uncovered a tripartite organization: two aggregation-promoting domains surround a regulatory module that affects interaction with the actin cytoskeleton. In all, our data provide direct evidence that CPEB3 is a functional prion in the mammalian brain and underline the potential importance of an actin/CPEB3 feedback loop for the synaptic plasticity underlying the persistence of long-term memory.
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Stephan
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Fioriti
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Nayan
authors.initials: N
authors.lastname: Lamba
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Colnaghi
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Karl
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA. Electronic address: irina.derkatch@gmail.com.
authors.forename: Irina L
authors.initials: IL
authors.lastname: Derkatch
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Kavli Institute for Brain Science, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA. Electronic address: erk5@columbia.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D017353:Gene Deletion; D051379:Mice; D011328:Prions / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: C477603:Cpeb3 protein, mouse; D011328:Prions; D016601:RNA-Binding Proteins