ArticleProceedings of the National Academy of Sciences of the United States of America2015
Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 83 citations in OpenAlex.
- Article
- Article
- FMRP-dependent translational control negatively regulates adapter protein complex 2-mediated endocytosis.iScience · 2025Article
- Proteomics insights into fragile X syndrome: Unraveling molecular mechanisms and therapeutic avenues.Neurobiology of disease · 2024Review
- On-Tissue Spatial Proteomics Integrating MALDI-MS Imaging with Shotgun Proteomics Reveals Soy Consumption-Induced Protein Changes in a Fragile X Syndrome Mouse Model.ACS chemical neuroscience · 2024Article
- Cell-Type-Specific Neuroproteomics of Synapses.Biomolecules · 2023Review
- Axonal and presynaptic FMRP: Localization, signal, and functional implications.Hearing research · 2023Review
- Rescue of neuropsychiatric phenotypes in a mouse model of 16p11.2 duplication syndrome by genetic correction of an epilepsy network hub.Nature communications · 2023Article
- Impaired synaptic incorporation of AMPA receptors in a mouse model of fragile X syndrome.Frontiers in molecular neuroscience · 2023Article
- Comparing synaptic proteomes across five mouse models for autism reveals converging molecular similarities including deficits in oxidative phosphorylation and Rho GTPase signaling.Frontiers in aging neuroscience · 2023Article
- Integrative omics indicate FMRP sequesters mRNA from translation and deadenylation in human neuronal cells.Molecular cell · 2022Article
- SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice.Cell death & disease · 2022Article
- Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome.Nature communications · 2022Article
- Review
- Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice.Brain : a journal of neurology · 2022Article
- SIPA1L1/SPAR1 Interacts with the Neurabin Family of Proteins and is Involved in GPCR Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Dysregulation of GABAA Receptor-Mediated Neurotransmission during the Auditory Cortex Critical Period in the Fragile X Syndrome Mouse Model.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome.International journal of molecular sciences · 2021Article
- Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis.Theranostics · 2021Article
- 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
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by severe intellectual disability and other symptoms including autism. Although caused by the silencing of a single gene, Fmr1 (fragile X mental retardation 1), the complexity of FXS pathogenesis is amplified because the encoded protein, FMRP, regulates the activity-dependent translation of numerous mRNAs. Although the mRNAs that associate with FMRP have been extensively studied, little is known regarding the proteins whose expression levels are altered, directly or indirectly, by loss of FMRP during brain development. Here we systematically measured protein expression in neocortical synaptic fractions from Fmr1 knockout (KO) and wild-type (WT) mice at both adolescent and adult stages. Although hundreds of proteins are up-regulated in the absence of FMRP in young mice, this up-regulation is largely diminished in adulthood. Up-regulated proteins included previously unidentified as well as known targets involved in synapse formation and function and brain development and others linked to intellectual disability and autism. Comparison with putative FMRP target mRNAs and autism susceptibility genes revealed substantial overlap, consistent with the idea that the autism endophenotype of FXS is due to a "multiple hit" effect of FMRP loss, particularly within the PSD95 interactome. Through studies of de novo protein synthesis in primary cortical neurons from KO and WT mice, we found that neurons lacking FMRP produce nascent proteins at higher rates, many of which are synaptic proteins and encoded by FMRP target mRNAs. Our results provide a greatly expanded view of protein changes in FXS and identify age-dependent effects of FMRP in shaping the neuronal proteome.
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