Abstract
Activity-dependent local translation of dendritic mRNAs is one process that underlies synaptic plasticity. Here, we demonstrate that several of the factors known to control polyadenylation-induced translation in early vertebrate development [cytoplasmic polyadenylation element-binding protein (CPEB), maskin, poly(A) polymerase, cleavage and polyadenylation specificity factor (CPSF) and Aurora] also reside at synaptic sites of rat hippocampal neurons. The induction of polyadenylation at synapses is mediated by the N-methyl-D-aspartate (NMDA) receptor, which transduces a signal that results in the activation of Aurora kinase. This kinase in turn phosphorylates CPEB, an essential RNA-binding protein, on a critical residue that is necessary for polyadenylation-induced translation. These data demonstrate a remarkable conservation of the regulatory machinery that controls signal-induced mRNA translation, and elucidates an axis connecting the NMDA receptor to localized protein synthesis at synapses.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Aurora Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / genetics*
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Female
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Hippocampus / physiology
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Molecular Sequence Data
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Oocytes / physiology
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Phosphorylation
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Polyadenylation / physiology
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Protein Serine-Threonine Kinases / physiology*
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RNA, Messenger / metabolism
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RNA-Binding Proteins / metabolism*
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Rats
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Receptors, N-Methyl-D-Aspartate / physiology*
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Signal Transduction / physiology*
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Synapses / physiology*
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Transcription Factors / metabolism*
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Xenopus / physiology
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Xenopus Proteins*
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mRNA Cleavage and Polyadenylation Factors*
Substances
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Cpeb1 protein, Xenopus
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RNA, Messenger
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RNA-Binding Proteins
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Receptors, N-Methyl-D-Aspartate
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Transcription Factors
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Xenopus Proteins
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mRNA Cleavage and Polyadenylation Factors
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Aurora Kinases
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases