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Fragile X mental retardation protein: Nucleocytoplasmic shuttling and association with somatodendritic ribosomes.
Open accessAbstract
Fragile X syndrome, a leading cause of inherited mental retardation, is attributable to the unstable expansion of a CGG-repeat within the FMR1 gene that results in the absence of the encoded protein. The fragile X mental retardation protein (FMRP) is a ribosome-associated RNA-binding protein of uncertain function that contains nuclear localization and export signals. We show here detailed cellular localization studies using both biochemical and immunocytochemical approaches. FMRP was highly expressed in neurons but not glia throughout the rat brain, as detected by light microscopy. Although certain structures, such as hippocampus, revealed a strong signal, the regional variation in staining intensity appeared to be related to neuron size and density. In human cell lines and mouse brain, FMRP co-fractionated primarily with polysomes and rough endoplasmic reticulum. Ultrastructural studies in rat brain revealed high levels of FMRP immunoreactivity in neuronal perikarya, where it is concentrated in regions rich in ribosomes, particularly near or between rough endoplasmic reticulum cisternae. Immunogold studies also provided evidence of nucleocytoplasmic shuttling of FMRP, which was localized in neuronal nucleoplasm and within nuclear pores. Moreover, labeling was observed in large- and small-caliber dendrites, in dendritic branch points, at the origins of spine necks, and in spine heads, all known locations of neuronal polysomes. Dendritic localization, which was confirmed by co-fractionation of FMRP with synaptosomal ribosomes, suggests a possible role of FMRP in the translation of proteins involved in dendritic structure or function and relevant for the mental retardation occurring in fragile X syndrome.
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“FMRP acts as an overall suppressor of protein synthesis (Laggerbauer et al., 2001), a function which it achieves by regulating nuclear-cytoplasmic translocation (Feng et al., 1997; Kim et al., 2009) and translation of various mRNAs. Many of these RNAs are associated with synapse function (Darnell et al., 2011).”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Feng et al., 1997
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FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072
The mGluR theory of fragile X mental retardation
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Self-citationFragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
Bassell, G. J., & Warren, S. T. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.004 · Cited by 1,051
Self-citation
Metadata
- Authors
- Feng, Y., Gutekunst, C.-A., Eberhart, D. E., Yi, H., Warren, S. T., & Hersch, S. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Emory University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-03-01
- Volume
- 17
- Issue
- 5
- Pages
- 1539-1547
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573369
- OpenAlex
- W2132943956
- Cited by
- 532
- References
- 8
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 13 · 2023: 10 · 2022: 13 · 2021: 9 · 2020: 15 · 2019: 17 · 2018: 20 · 2017: 17 · 2016: 16 · 2015: 9 · 2014: 28 · 2013: 31 · 2012: 23
- FWCI
- 9.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5k08ns001624-04)
- National Institute of Neurological Disorders and Stroke (NS01624)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 20521, R01HD020521, R37HD020521)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- FMRP, fragile X syndrome, CGG repeat expansion, nucleocytoplasmic shuttling, polysomes, rough endoplasmic reticulum, nuclear pores, neuronal localization, dendritic spines
- MeSH terms
- Animals, Cell Line, Cell Nucleus, Cerebral Cortex, Cytoplasm, Dendrites, Fragile X Syndrome, Humans, Immunoenzyme Techniques, Immunohistochemistry, Male, Nerve Tissue Proteins, Neuroglia, Neurons, Ribosomes, RNA-Binding Proteins, Rats, Sprague-Dawley, Endoplasmic Reticulum, Rough, Trinucleotide Repeats, Mice, Rats, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1
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