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Citation
Khan, M.R., Li, L., Pérez-Sánchez, C., Saraf, A., Florens, L., Slaughter, B.D., Unruh, J.R., Si, K. (2015). Amyloidogenic Oligomerization Transforms Drosophila Orb2 from a Translation Repressor to an Activator.  Cell 163(6): 1468--1483.
FlyBase ID
FBrf0230300
Publication Type
Research paper
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.
Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC4674814 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell
    Title
    Cell
    Publication Year
    1974-
    ISBN/ISSN
    0092-8674
    Data From Reference
    Alleles (20)
    Genes (40)
    Physical Interactions (21)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (5)
    Transgenic Constructs (17)