Abstract
Local translation of proteins in distal dendrites is thought to support synaptic structural plasticity. We have previously shown that metabotropic glutamate receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering rapid association of some mRNAs with translation machinery near synapses, and leading to protein synthesis. To determine the identity of these mRNAs, a cDNA library produced from distal nerve processes was used to screen synaptic polyribosome-associated mRNA. We identified mRNA for the fragile X mental retardation protein (FMRP) in these processes by use of synaptic subcellular fractions, termed synaptoneurosomes. We found that this mRNA associates with translational complexes in synaptoneurosomes within 1-2 min after mGluR1 stimulation of this preparation, and we observed increased expression of FMRP after mGluR1 stimulation. In addition, we found that FMRP is associated with polyribosomal complexes in these fractions. In vivo, we observed FMRP immunoreactivity in spines, dendrites, and somata of the developing rat brain, but not in nuclei or axons. We suggest that rapid production of FMRP near synapses in response to activation may be important for normal maturation of synaptic connections.
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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Antibodies / pharmacology
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Antisense Elements (Genetics)
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Brain / growth & development
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Brain / metabolism
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DNA, Complementary
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Dendrites / physiology
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Dendrites / ultrastructure
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Excitatory Amino Acid Antagonists / pharmacology
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Fragile X Mental Retardation Protein
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Gene Library
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Humans
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Kinetics
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Molecular Sequence Data
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / genetics
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Neurons / metabolism*
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Neurotransmitter Agents / physiology
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Oligonucleotide Probes
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Organ Specificity
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Polyribosomes / metabolism
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Protein Biosynthesis* / drug effects
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RNA, Messenger / metabolism
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / metabolism
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Rats
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Receptors, Metabotropic Glutamate / physiology
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Resorcinols / pharmacology
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Sequence Homology, Amino Acid
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Synapses / drug effects
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Synapses / physiology*
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Synapses / ultrastructure
Substances
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Antibodies
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Antisense Elements (Genetics)
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DNA, Complementary
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Excitatory Amino Acid Antagonists
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FMR1 protein, human
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FXR1 protein, human
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FXR2 protein, human
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Fmr1 protein, rat
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Nerve Tissue Proteins
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Neurotransmitter Agents
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Oligonucleotide Probes
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RNA, Messenger
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RNA-Binding Proteins
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Receptors, Metabotropic Glutamate
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Resorcinols
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metabotropic glutamate receptor type 1
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Fragile X Mental Retardation Protein
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3,5-dihydroxyphenylglycine
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Glycine