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Drosophila CPEB Orb2A mediates memory independent of Its RNA-binding domain.
- Source :
-
Neuron [Neuron] 2012 Oct 18; Vol. 76 (2), pp. 383-95. Date of Electronic Publication: 2012 Oct 17. - Publication Year :
- 2012
-
Abstract
- Long-term memory and synaptic plasticity are thought to require the synthesis of new proteins at activated synapses. The CPEB family of RNA binding proteins, including Drosophila Orb2, has been implicated in this process. The precise mechanism by which these molecules regulate memory formation is however poorly understood. We used gene targeting and site-specific transgenesis to specifically modify the endogenous orb2 gene in order to investigate its role in long-term memory formation. We show that the Orb2A and Orb2B isoforms, while both essential, have distinct functions in memory formation. These two isoforms have common glutamine-rich and RNA-binding domains, yet Orb2A uniquely requires the former and Orb2B the latter. We further show that Orb2A induces Orb2 complexes in a manner dependent upon both its glutamine-rich region and neuronal activity. We propose that Orb2B acts as a conventional CPEB to regulate transport and/or translation of specific mRNAs, whereas Orb2A acts in an unconventional manner to form stable Orb2 complexes that are essential for memory to persist.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Animals, Genetically Modified
Biogenic Amines administration & dosage
Brain metabolism
Brain ultrastructure
Cell Line
Chromatography, High Pressure Liquid
Courtship
Drosophila
Drosophila Proteins classification
Drosophila Proteins genetics
Embryo, Nonmammalian
Gene Expression Regulation, Developmental genetics
Genotype
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Immunoprecipitation
Larva
Learning physiology
Male
Mass Spectrometry
Microscopy, Immunoelectron
Mitogen-Activated Protein Kinases genetics
Mushroom Bodies cytology
Mushroom Bodies metabolism
Mutation genetics
Protein Isoforms genetics
Protein Structure, Tertiary physiology
RNA genetics
RNA, Messenger metabolism
Transcription Factors classification
Transcription Factors genetics
mRNA Cleavage and Polyadenylation Factors classification
mRNA Cleavage and Polyadenylation Factors genetics
Drosophila Proteins metabolism
Memory physiology
Protein Isoforms metabolism
RNA metabolism
RNA-Binding Proteins physiology
Transcription Factors metabolism
mRNA Cleavage and Polyadenylation Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 76
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 23083740
- Full Text :
- https://doi.org/10.1016/j.neuron.2012.08.028