Abstract
The dendritic trafficking of RNA binding proteins (RBPs) is an important posttranscriptional process involved in the regulation of synaptic plasticity. For example, HuD RBP binds to AU-rich elements (AREs) in the 3' untranslated regions (3'UTR) of immediate-early gene (IEG) transcripts, whose protein products directly affect synaptic plasticity. However, the subcellular localization of HuD RBPs and associated mRNAs has not been investigated following neuronal stimulation. Immunofluorescence analysis revealed activity-dependent dendritic localization of HuD RBPs following KCl stimulation in hippocampal neurons, while immunoprecipitation demonstrated the association of HuD RBP with neuronal mRNAs encoding neuritin, Homer1a, GAP-43, Neuroligins, Verge and CAMKIIalpha. Activity-dependent expression of HuD involves activation of NMDAR as NMDA receptor 1 knockout mice (Nr1(neo-/-)) exhibited decreased expression of HuD. Moreover, translational regulation of HuD-associated transcripts was suggested by its co-localization with poly-A-binding protein (PABP) as well as the cap-binding protein (eIF4E). We propose that post-transcriptional regulation of neuronal mRNAs by HuD RBPs mediates protein synthesis-dependent changes in synaptic plasticity.
MeSH terms
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3' Untranslated Regions / metabolism
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Animals
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Antibody Specificity / drug effects
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Antibody Specificity / radiation effects
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Cross-Linking Reagents / pharmacology
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Cytoplasmic Granules / drug effects
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Cytoplasmic Granules / metabolism
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Cytoplasmic Granules / radiation effects
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Dendrites / drug effects
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Dendrites / metabolism
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Dendrites / radiation effects
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ELAV Proteins / metabolism*
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GAP-43 Protein / genetics
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GAP-43 Protein / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / radiation effects
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Hippocampus / cytology
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Membrane Potentials / drug effects
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Membrane Potentials / radiation effects
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Mice
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / radiation effects
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Polyribosomes / drug effects
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Polyribosomes / metabolism
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Polyribosomes / radiation effects
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Potassium Chloride / pharmacology
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Protein Transport / drug effects
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Protein Transport / radiation effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Subcellular Fractions / drug effects
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Subcellular Fractions / metabolism
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Ultraviolet Rays
Substances
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3' Untranslated Regions
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Cross-Linking Reagents
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ELAV Proteins
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GAP-43 Protein
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RNA, Messenger
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Potassium Chloride
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Calcium-Calmodulin-Dependent Protein Kinase Type 2