title: SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3.
abstract: Protein synthesis is crucial for the maintenance of long-term-memory-related synaptic plasticity. The prion-like cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. Here, we provide evidence that the prion-like aggregation and activity of CPEB3 is controlled by SUMOylation. In the basal state, CPEB3 is a repressor and is soluble. Under these circumstances, CPEB3 is SUMOylated in hippocampal neurons both in vitro and in vivo. Following neuronal stimulation, CPEB3 is converted into an active form that promotes the translation of target mRNAs, and this is associated with a decrease of SUMOylation and an increase of aggregation. A chimeric CPEB3 protein fused to SUMO cannot form aggregates and cannot activate the translation of target mRNAs. These findings suggest a model whereby SUMO regulates translation of mRNAs and structural synaptic plasticity by modulating the aggregation of the prion-like protein CPEB3.
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Drisaldi
authors.affiliation: Department of Neuroscience, 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: Luana
authors.initials: L
authors.lastname: Fioriti
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Nishta
authors.initials: N
authors.lastname: Rao
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Myers
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Snyder
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Metzger
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Tarasoff
authors.affiliation: Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Konstantinov
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON 4KD481, Canada.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Manley
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: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D011328:Prions / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism; D058207:Sumoylation
chemical_list: C477603:Cpeb3 protein, mouse; D011328:Prions; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins