Cited by 211Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchRNA and protein synthesis mechanisms

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Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses

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Weiler, Ivan Jeanne, Spangler, Chad C., Klintsova, Anna Y., Grossman, Aaron W., Kim, Soong Ho, Bertaina-Anglade, Valerie, Khaliq, Hooma, de Vries, Froukje E., Lambers, Femke A. E., Hatia, Fatima, Base, Christine K., Greenough, William T.·2004·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0407533101PMC PMC536018

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Abstract

Fragile X mental retardation is caused by absence of the RNA-binding protein fragile X mental retardation protein (FMRP), encoded by the FMR1 gene. There is increasing evidence that FMRP regulates transport and modulates translation of some mRNAs. We studied neurotransmitter-activated synaptic protein synthesis in fmr1 -knockout mice. Synaptoneurosomes from knockout mice did not manifest accelerated polyribosome assembly or protein synthesis as it occurs in wild-type mice upon stimulation of group I metabotropic glutamate receptors. Direct activation of protein kinase C did not compensate in the knockout mouse, indicating that the FMRP-dependent step is further along the signaling pathway. Visual cortices of young knockout mice exhibited a lower proportion of dendritic spine synapses containing polyribosomes than did the cortices of wild-type mice, corroborating this finding in vivo . This deficit in rapid neurotransmitter-controlled local translation of specific proteins may contribute to morphological and functional abnormalities observed in patients with fragile X syndrome.

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Authors: Weiler, I. J., Spangler, C. C., Klintsova, A. Y., Grossman, A. W., Kim, S. H., Bertaina-Anglade, V., Khaliq, H., de Vries, F. E., Lambers, F. A. E., Hatia, F., Base, C. K., & Greenough, W. T.
Affiliations: University of Illinois Urbana-Champaign (US)
Beckman Institute, Neuroscience Program, and Departments of Psychology, Psychiatry, and Cell and Structural Biology, University of Illinois at Urbana–Champaign, Urbana, IL 61801
ORCID: Klintsova, Anna Y.
Grossman, Aaron W.
de Vries, Froukje E.
Lambers, Femke A. E.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2004-11-17
Volume: 101
Issue: 50
Pages: 17504-17509
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0407533101
PMC: PMC536018
OpenAlex: W2007532395
Cited by: 210
References: 52
Citations by year: 2025: 1 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 10 · 2014: 7 · 2013: 7 · 2012: 16
FWCI: 11.25
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: FRAXA Research Foundation (MH35321)
Universiteit Antwerpen
National Institutes of Health (5r03hd035565-02, 5r01hd037175-03)
National Institute of Mental Health (MH-35321, R01MH035321, R37MH035321)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03 HD 35565-01, HD 37175)
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, fragile X syndrome, FMR1 gene, synaptic protein synthesis, local translation, group I metabotropic glutamate receptors, protein kinase C, dendritic spines, synaptoneurosomes, visual cortex, Fmr1 knockout mice, RNA-binding proteins
MeSH terms: Animals, Glycine, Methionine, Microscopy, Electron, Nerve Tissue Proteins, Potassium, Resorcinols, Ribosomes, Synapses, Protein Biosynthesis, RNA-Binding Proteins, Gene Deletion, Mice, Knockout, Neurotransmitter Agents, Mice, Fragile X Messenger Ribonucleoprotein 1, Fragile X Mental Retardation Protein

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Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses

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