Cited by 644Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchRNA and protein synthesis mechanisms

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Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation

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Weiler, Ivan Jeanne, Irwin, Scott A., Klintsova, Anna Y., Spencer, Corinne M., Brazelton, Anthony D., Miyashiro, Kevin, Comery, Thomas A., Patel, Bindu, Eberwine, James, Greenough, William T.·1997·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.94.10.5395PMC PMC24689

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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.

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How mRNA transport in nerve cells influences synapses and learning
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Glycogen Synthase Kinase-3: Abnormalities and Therapeutic Potential in Fragile X Syndrome
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Development of a Viral Toolbox to Study the Role of m6A RNA Methylation in Memory
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“I was literally brought into the field as a pre-reviewer of the classic paper from the Greenough laboratory showing that the messenger RNA for the fragile X mental retardation protein is found in and translated in synaptoneurosomes in response to metabotropic glutamate receptor (mGluR) stimulation (Weiler et al. 1997).”
Background
A drosophila model of cellular and molecular mechanisms of fragile x syndrome.
Pan, L. (2007)
Fragile X syndrome
Martin, G. E., Bush, L. C., Patel, S. P., & Losh, M. C. (2021) · Springer eBooks · doi:10.1007/978-3-030-74985-9_4

Authors: Weiler, I. J., Irwin, S. A., Klintsova, A. Y., Spencer, C. M., Brazelton, A. D., Miyashiro, K., Comery, T. A., Patel, B., Eberwine, J., & Greenough, W. T.
Affiliations: University of Illinois Urbana-Champaign (US)
ORCID: Irwin, Scott A.
Klintsova, Anna Y.
Spencer, Corinne M.
Eberwine, James
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1997-05-13
Volume: 94
Issue: 10
Pages: 5395-5400
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.94.10.5395
PMC: PMC24689
OpenAlex: W2002760096
Cited by: 644
References: 58
Citations by year: 2026: 2 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 11 · 2021: 12 · 2020: 8 · 2019: 14 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 23 · 2014: 24 · 2013: 27 · 2012: 29
FWCI: 12.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: FRAXA Research Foundation (MH35321)
John D. and Catherine T. MacArthur Foundation
National Institutes of Health
U.S. Public Health Service
National Institute on Aging (AG10154, R01AG010154)
National Institute of Mental Health (MH-35321, R01MH035321, R37MH035321)
National Center for Research Resources (RR 04050, P41RR004050)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: FMRP, local protein synthesis, metabotropic glutamate receptor 1, polysomes, synaptoneurosomes, dendritic mRNA, synapse maturation, synaptic plasticity, dendritic translation
MeSH terms: Amino Acid Sequence, Animals, Antibodies, Brain, Dendrites, Glycine, Humans, Kinetics, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Organ Specificity, Polyribosomes, Resorcinols, RNA, Messenger, Synapses, Protein Biosynthesis, Oligonucleotide Probes, Gene Library, Antisense Elements (Genetics), RNA-Binding Proteins, Sequence Homology, Amino Acid, DNA, Complementary, Receptors, Metabotropic Glutamate, Neurotransmitter Agents, Excitatory Amino Acid Antagonists, Rats, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1

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Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation

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