Amyloidogenic Oligomerization Transforms Drosophila Orb2 from a Translation Repressor to an Activator
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..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:163 |
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| Enthalten in: |
Cell - 163(2015), 6, Seite 1468-1483 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khan, Mohammed Repon [VerfasserIn] |
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| doi: |
10.1016/j.cell.2015.11.020 |
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| 100 | 1 | |a Khan, Mohammed Repon |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Amyloidogenic Oligomerization Transforms Drosophila Orb2 from a Translation Repressor to an Activator |
| 264 | 1 | |c 2015 | |
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| 520 | |a 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. | ||
| 540 | |a Nutzungsrecht: Copyright © 2015 Elsevier Inc. All rights reserved. | ||
| 540 | |a © COPYRIGHT 2015 Elsevier B.V. | ||
| 650 | 4 | |a Amyloidogenic Proteins - chemistry | |
| 650 | 4 | |a Serine Endopeptidases - genetics | |
| 650 | 4 | |a Drosophila Proteins - chemistry | |
| 650 | 4 | |a Drosophila melanogaster - metabolism | |
| 650 | 4 | |a mRNA Cleavage and Polyadenylation Factors - metabolism | |
| 650 | 4 | |a mRNA Cleavage and Polyadenylation Factors - chemistry | |
| 650 | 4 | |a Amyloidogenic Proteins - metabolism | |
| 650 | 4 | |a RNA-Binding Proteins - metabolism | |
| 650 | 4 | |a Transcription Factors - chemistry | |
| 650 | 4 | |a Transcription Factors - metabolism | |
| 650 | 4 | |a Drosophila Proteins - metabolism | |
| 650 | 4 | |a Drosophila Proteins - genetics | |
| 650 | 4 | |a Protein biosynthesis | |
| 650 | 4 | |a RNA | |
| 650 | 4 | |a Analysis | |
| 650 | 4 | |a Genetic translation | |
| 650 | 4 | |a Oligomers | |
| 650 | 4 | |a Drosophila | |
| 650 | 4 | |a Protein binding | |
| 700 | 1 | |a Li, Liying |4 oth | |
| 700 | 1 | |a Pérez-Sánchez, Consuelo |4 oth | |
| 700 | 1 | |a Saraf, Anita |4 oth | |
| 700 | 1 | |a Florens, Laurence |4 oth | |
| 700 | 1 | |a Slaughter, Brian D |4 oth | |
| 700 | 1 | |a Unruh, Jay R |4 oth | |
| 700 | 1 | |a Si, Kausik |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Cell |d Cambridge, Mass. : Cell Press, 1974 |g 163(2015), 6, Seite 1468-1483 |w (DE-627)129403725 |w (DE-600)187009-9 |w (DE-576)014785382 |x 0092-8674 |7 nnns |
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| 856 | 4 | 1 | |u http://dx.doi.org/10.1016/j.cell.2015.11.020 |3 Volltext |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26638074 |
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