ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA promotes synapsin phase separation providing a platform for local translation.bioRxiv : the preprint server for biology · 2026Article
- Molecular switch of the dendrite-to-spine transport of TDP-43/FMRP-bound neuronal mRNAs and its impairment in ASD.Cellular & molecular biology letters · 2025Article
- Review
- The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.EMBO reports · 2024Article
- Dissecting 16p11.2 hemi-deletion to study sex-specific striatal phenotypes of neurodevelopmental disorders.Molecular psychiatry · 2024Article
- Glucose-derived glutamate drives neuronal terminal differentiation in vitro.EMBO reports · 2024Article
- FMRP phosphorylation and interactions with Cdh1 regulate association with dendritic RNA granules and MEF2-triggered synapse elimination.Neurobiology of disease · 2023Article
- Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes.Nature communications · 2023Article
- Maternal Diabetes Deregulates the Expression of Mecp2 via miR-26b-5p in Mouse Embryonic Neural Stem Cells.Cells · 2023Article
- FMRP, FXR1 protein and Dlg4 mRNA, which are associated with fragile X syndrome, are involved in the ubiquitin-proteasome system.Scientific reports · 2023Article
- Adaptive control of synaptic plasticity integrates micro- and macroscopic network function.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Development of single-molecule ubiquitination mediated fluorescence complementation to visualize protein ubiquitination dynamics in dendrites.Cell reports · 2022Article
- The role of altered translation in intellectual disability and epilepsy.Progress in neurobiology · 2022Review
- Next generation single-molecule techniques: Imaging, labeling, and manipulation in vitro and in cellulo.Molecular cell · 2022Review
- FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons.eLife · 2021Article
- Axonal mRNA localization and local translation in neurodegenerative disease.Neural regeneration research · 2021Review
- Intracellular mRNA transport and localized translation.Nature reviews. Molecular cell biology · 2021Review
- FMRP Interacts with RARα in Synaptic Retinoic Acid Signaling and Homeostatic Synaptic Plasticity.International journal of molecular sciences · 2021Article
- Differential regulation of local mRNA dynamics and translation following long-term potentiation and depression.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS.
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