Abstract
Neuronal development, plasticity and survival require activity-dependent synapse-to-nucleus signaling. Most studies implicate an activity-dependent regulation of gene expression in this phenomenon. However, little is known about other nuclear functions that are regulated by synaptic activity. Here we show that a newly identified component of rat postsynaptic densities (PSDs), AIDA-1d, can regulate global protein synthesis by altering nucleolar numbers. AIDA-1d binds to the first two postsynaptic density-95/Discs large/zona occludens-1 (PDZ) domains of the scaffolding protein PSD-95 via its C-terminal three amino acids. Stimulation of NMDA receptors (NMDARs), which are also bound to PSD-95, results in a Ca2+-independent translocation of AIDA-1d to the nucleus, where it couples to Cajal bodies and induces Cajal body-nucleolar association. Long-term neuronal stimulation results in an AIDA-1-dependent increase in nucleolar numbers and protein synthesis. We propose that AIDA-1d mediates a link between synaptic activity and control of protein biosynthetic capacity by regulating nucleolar assembly.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cell Nucleolus / drug effects
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Cell Nucleolus / metabolism*
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Cells, Cultured
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Disks Large Homolog 4 Protein
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Green Fluorescent Proteins / metabolism
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Humans
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Immunoprecipitation
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / metabolism
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N-Methylaspartate / pharmacology
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Neurons / drug effects
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Neurons / physiology*
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Neurons / ultrastructure*
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Phosphoproteins / metabolism
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / physiology*
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Protein Structure, Tertiary
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Protein Transport / drug effects
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RNA, Small Interfering / pharmacology
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Rats
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Signal Transduction / physiology*
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Synapses / metabolism
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Transfection / methods
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Zonula Occludens-1 Protein
Substances
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Adaptor Proteins, Signal Transducing
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Phosphoproteins
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RNA, Small Interfering
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TJP1 protein, human
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Tjp1 protein, rat
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Zonula Occludens-1 Protein
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Green Fluorescent Proteins
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N-Methylaspartate