ArticleThe Journal of biological chemistry2009
Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 150 citations in OpenAlex.
- Age-Related Decline in Dendritic Architecture of Hippocampal CA1 Principal Neurons in a Mouse Model of Fragile X Syndrome.Developmental neurobiology · 2026Article
- Gene Therapy for Fragile X Syndrome, Challenges, and Promises.The journal of gene medicine · 2025Review
- Cage effects on synaptic plasticity and its modulation in a mouse model of fragile X syndrome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Early expression of GluN2A-containing NMDA receptors in a model of fragile X syndrome.Journal of neurophysiology · 2024Article
- The multifaceted role of Fragile X-Related Protein 1 (FXR1) in cellular processes: an updated review on cancer and clinical applications.Cell death & disease · 2024Review
- Review
- A genetic labeling system to study dendritic spine development in zebrafish models of neurodevelopmental disorders.Disease models & mechanisms · 2022Article
- Review
- Review
- Inherited unbalanced translocation (4p16.3p15.32 duplication/8p23.3p23.2deletion) in the four generation pedigree with intellectual disability/developmental delay.Molecular cytogenetics · 2021Article
- Channelopathies in fragile X syndrome.Nature reviews. Neuroscience · 2021Review
- Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/β-catenin, and mTOR signaling during corticogenesis.Molecular brain · 2020Article
- FMRP(1-297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome.Nature communications · 2020Article
- FUS Recognizes G Quadruplex Structures Within Neuronal mRNAs.Frontiers in molecular biosciences · 2020Article
- Transient Enhanced GluA2 Expression in Young Hippocampal Neurons of a Fragile X Mouse Model.Frontiers in synaptic neuroscience · 2020Article
- Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.Neuron · 2019Review
- Widespread Alterations in Translation Elongation in the Brain of Juvenile Fmr1 Knockout Mice.Cell reports · 2019Article
- Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice.Translational psychiatry · 2019Article
- Calsyntenin-1 Negatively Regulates ICAM5 Accumulation in Postsynaptic Membrane and Influences Dendritic Spine Maturation in a Mouse Model of Fragile X Syndrome.Frontiers in neuroscience · 2019Article
- Inhibition of GluN2A NMDA receptors ameliorates synaptic plasticity deficits in the Fmr1The Journal of physiology · 2018Article
18 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional absence of fragile X mental retardation protein (FMRP) causes the fragile X syndrome, a hereditary form of mental retardation characterized by a change in dendritic spine morphology. The RNA-binding protein FMRP has been implicated in regulating postsynaptic protein synthesis. Here we have analyzed whether the abundance of scaffold proteins and neurotransmitter receptor subunits in postsynaptic densities (PSDs) is altered in the neocortex and hippocampus of FMRP-deficient mice. Whereas the levels of several PSD components are unchanged, concentrations of Shank1 and SAPAP scaffold proteins and various glutamate receptor subunits are altered in both adult and juvenile knock-out mice. With the exception of slightly increased hippocampal SAPAP2 mRNA levels in adult animals, altered postsynaptic protein concentrations do not correlate with similar changes in total and synaptic levels of corresponding mRNAs. Thus, loss of FMRP in neurons appears to mainly affect the translation and not the abundance of particular brain transcripts. Semi-quantitative analysis of RNA levels in FMRP immunoprecipitates showed that in the mouse brain mRNAs encoding PSD components, such as Shank1, SAPAP1-3, PSD-95, and the glutamate receptor subunits NR1 and NR2B, are associated with FMRP. Luciferase reporter assays performed in primary cortical neurons from knock-out and wild-type mice indicate that FMRP silences translation of Shank1 mRNAs via their 3'-untranslated region. Activation of metabotropic glutamate receptors relieves translational suppression. As Shank1 controls dendritic spine morphology, our data suggest that dysregulation of Shank1 synthesis may significantly contribute to the abnormal spine development and function observed in brains of fragile X syndrome patients.
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