ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Evidence for a fragile X mental retardation protein-mediated translational switch in metabotropic glutamate receptor-triggered Arc translation and long-term depression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 155 citations in OpenAlex.
- ATF4 Modulates Group 1 mGluR-Dependent molecular signaling, hippocampal plasticity and behavior.Molecular psychiatry · 2026Article
- FMRP regulates neuronal RNA granules containing stalled ribosomes, not where ribosomes stall.eLife · 2026Article
- Dysfunctional neural dynamics associated with sensory phenotypes in Fragile X syndrome: insights from mouse models.Journal of neurodevelopmental disorders · 2025Review
- Translation stalling in neurons: a critical mechanism for timely protein delivery to distal cellular processes.Biochemical Society transactions · 2025Article
- Article
- Construction destruction: Contribution of dyregulated proteostasis to neurodevelopmental disorders.Current opinion in neurobiology · 2025Review
- Behavioral benefits of GSK-3β inhibition and state-dependent microtubule signatures in theFrontiers in neuroscience · 2025Article
- FMR1 genetically interacts with DISC1 to regulate glutamatergic synaptogenesis.Schizophrenia (Heidelberg, Germany) · 2024Article
- Deciphering autism heterogeneity: a molecular stratification approach in four mouse models.Translational psychiatry · 2024Article
- mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.EMBO molecular medicine · 2024Article
- Phencyclidine Disrupts Neural Coordination and Cognitive Control by Dysregulating Translation.Biological psychiatry global open science · 2024Article
- FMRP phosphorylation and interactions with Cdh1 regulate association with dendritic RNA granules and MEF2-triggered synapse elimination.Neurobiology of disease · 2023Article
- Characterization of Fragile X Mental Retardation Protein expression in human nociceptors and their axonal projections to the spinal dorsal horn.The Journal of comparative neurology · 2023Article
- Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation.Biomedicines · 2023Review
- Blockade of Type 2A Protein Phosphatase Signaling Attenuates Complement C1q-Mediated Microglial Phagocytosis of Glutamatergic Synapses Induced by Amyloid Fibrils.Molecular neurobiology · 2023Article
- Activity-regulated cytoskeletal-associated protein (Arc) in presynaptic terminals and extracellular vesicles in hippocampal synapses.Frontiers in molecular neuroscience · 2023Article
- Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2022Review
- The role of altered translation in intellectual disability and epilepsy.Progress in neurobiology · 2022Review
- Intercepting IRE1 kinase-FMRP signaling prevents atherosclerosis progression.EMBO molecular medicine · 2022Article
- Regulation of Metabotropic Glutamate Receptor Internalization and Synaptic AMPA Receptor Endocytosis by the Postsynaptic Protein Norbin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Group 1 metabotropic glutamate receptor (mGluR)-stimulated protein synthesis and long-term synaptic depression (mGluR-LTD) are altered in the mouse model of fragile X syndrome, Fmr1 knock-out (KO) mice. Fmr1 encodes fragile X mental retardation protein (FMRP), a dendritic RNA binding protein that functions, in part, as a translational suppressor. It is unknown whether and how FMRP acutely regulates LTD and/or the rapid synthesis of new proteins required for LTD, such as the activity-regulated cytoskeletal-associated protein (Arc). The protein phosphatase PP2A dephosphorylates FMRP, which contributes to translational activation of some target mRNAs. Here, we report that PP2A and dephosphorylation of FMRP at S500 are required for an mGluR-induced, rapid (5 min) increase in dendritic Arc protein and LTD in rat and mouse hippocampal neurons. In Fmr1 KO neurons, basal, dendritic Arc protein levels and mGluR-LTD are enhanced, but mGluR-triggered Arc synthesis is absent. Lentiviral-mediated expression of wild-type FMRP in Fmr1 KO neurons suppresses basal dendritic Arc levels and mGluR-LTD, and restores rapid mGluR-triggered Arc synthesis. A phosphomimic of FMRP (S500D) suppresses steady-state dendritic Arc levels but does not rescue mGluR-induced Arc synthesis. A dephosphomimic of FMRP (S500A) neither suppresses dendritic Arc nor supports mGluR-induced Arc synthesis. Accordingly, S500D-FMRP expression in Fmr1 KO neurons suppresses mGluR-LTD, whereas S500A-FMRP has no effect. These data support a model in which phosphorylated FMRP functions to suppress steady-state translation of Arc and LTD. Upon mGluR activation of PP2A, FMRP is rapidly dephosphorylated, which contributes to rapid new synthesis of Arc and mGluR-LTD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.