Abstract
Long-term synaptic plasticity involves changes in the expression and membrane insertion of cell-surface proteins. Interestingly, the mRNAs encoding many cell-surface proteins are localized to dendrites, but whether dendritic protein synthesis is required for activity-induced surface expression of specific proteins is unknown. Herein, we used microfluidic devices to demonstrate that dendritic protein synthesis is necessary for activity-induced insertion of GluN2A-containing NMDA receptors in rat hippocampal neurons. Furthermore, visualization of activity-induced local translation of GluN2A mRNA and membrane insertion of GluN2A protein in dendrites was directly observed and shown to depend on a 3' untranslated region cytoplasmic polyadenylation element and its associated translation complex. These findings uncover a novel mechanism for cytoplasmic polyadenylation element-mediated posttranscriptional regulation of GluN2A mRNA to control NMDA receptor surface expression during synaptic plasticity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Analysis of Variance
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Animals
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Anisomycin / pharmacology
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Binding Sites / genetics
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Biotinylation
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Cells, Cultured
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Dendrites / drug effects
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Dendrites / metabolism*
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Embryo, Mammalian
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Female
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Glycine / pharmacology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Hippocampus / cytology
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Immunoprecipitation
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Male
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Mice
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Mice, Inbred C57BL
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Microfluidic Analytical Techniques
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Mutagenesis, Insertional / physiology*
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / ultrastructure*
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Polyadenylation / genetics
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / metabolism*
Substances
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3' Untranslated Regions
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Nerve Tissue Proteins
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Protein Synthesis Inhibitors
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RNA, Messenger
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RNA, Small Interfering
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Receptors, N-Methyl-D-Aspartate
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Green Fluorescent Proteins
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Anisomycin
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Glycine
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N-methyl D-aspartate receptor subtype 2A