title: Amyloidogenic Oligomerization Transforms Drosophila Orb2 from a Translation Repressor to an Activator.
abstract: Memories are thought to be formed in response to transient experiences, in part through changes in local protein synthesis at synapses. In Drosophila, the amyloidogenic (prion-like) state of the RNA binding protein Orb2 has been implicated in long-term memory, but how conformational conversion of Orb2 promotes memory formation is unclear. Combining in vitro and in vivo studies, we find that the monomeric form of Orb2 represses translation and removes mRNA poly(A) tails, while the oligomeric form enhances translation and elongates the poly(A) tails and imparts its translational state to the monomer. The CG13928 protein, which binds only to monomeric Orb2, promotes deadenylation, whereas the putative poly(A) binding protein CG4612 promotes oligomeric Orb2-dependent translation. Our data support a model in which monomeric Orb2 keeps target mRNA in a translationally dormant state and experience-dependent conversion to the amyloidogenic state activates translation, resulting in persistent alteration of synaptic activity and stabilization of memory.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Mohammed Repon
authors.initials: MR
authors.lastname: Khan
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Liying
authors.initials: L
authors.lastname: Li
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Pérez-Sánchez
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Saraf
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: ksi@stowers.org.
authors.forename: Kausik
authors.initials: K
authors.lastname: Si
mesh_terms: D020413:3' Untranslated Regions; D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D057567:Memory, Long-Term; D051379:Mice; D026723:Polyadenylation; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D058227:Amyloidogenic Proteins; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; D012697:Serine Endopeptidases; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; C529066:Orb2 protein, Drosophila; C512782:Teq protein, Drosophila; C490387:Cpeb1 protein, mouse