title: Critical role of amyloid-like oligomers of Drosophila Orb2 in the persistence of memory.
abstract: A long-standing question in the study of long-term memory is how a memory trace persists for years when the proteins that initiated the process turn over and disappear within days. Previously, we postulated that self-sustaining amyloidogenic oligomers of cytoplasmic polyadenylation element-binding protein (CPEB) provide a mechanism for the maintenance of activity-dependent synaptic changes and, thus, the persistence of memory. Here, we found that the Drosophila CPEB Orb2 forms amyloid-like oligomers, and oligomers are enriched in the synaptic membrane fraction. Of the two protein isoforms of Orb2, the amyloid-like oligomer formation is dependent on the Orb2A form. A point mutation in the prion-like domain of Orb2A, which reduced amyloid-like oligomerization of Orb2, did not interfere with learning or memory persisting up to 24 hr. However the mutant flies failed to stabilize memory beyond 48 hr. These results support the idea that amyloid-like oligomers of neuronal CPEB are critical for the persistence of long-term memory.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Majumdar
authors.forename: Wanda Colón
authors.initials: WC
authors.lastname: Cesario
authors.forename: Erica
authors.initials: E
authors.lastname: White-Grindley
authors.forename: Huoqing
authors.initials: H
authors.lastname: Jiang
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Ren
authors.forename: Mohammed Repon
authors.initials: MR
authors.lastname: Khan
authors.forename: Liying
authors.initials: L
authors.lastname: Li
authors.forename: Edward Man-Lik
authors.initials: EM
authors.lastname: Choi
authors.forename: Kasthuri
authors.initials: K
authors.lastname: Kannan
authors.forename: Fengli
authors.initials: F
authors.lastname: Guo
authors.forename: Jay
authors.initials: J
authors.lastname: Unruh
authors.forename: Brian
authors.initials: B
authors.lastname: Slaughter
authors.forename: Kausik
authors.initials: K
authors.lastname: Si
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001048:Aplysia / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D008568:Memory; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D017354:Point Mutation; D020033:Protein Isoforms / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000682:Amyloid; D029721:Drosophila Proteins; C529066:Orb2 protein, Drosophila; D020033:Protein Isoforms; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors