ArticleNeurobiology of disease2013
Phosphorylation of FMRP and alterations of FMRP complex underlie enhanced mLTD in adult rats triggered by early life seizures.
Article in Neurobiology of disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Pooled it
- Early life seizures chronically disrupt L-type voltage gated calcium channel regulation of mGluR mediated long term depression via interactions with protein phosphatase 2A.Neurobiology of disease · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Article
- Increased degradation of FMRP contributes to neuronal hyperexcitability in tuberous sclerosis complex.Cell reports · 2023Article
- Article
- Augmented impulsive behavior in febrile seizure-induced mice.Toxicological research · 2023Article
- Autism spectrum disorder in the fragile X premutation state: possible mechanisms and implications.Journal of neurology · 2022Review
- Seizures in Fragile X Syndrome: Associations and Longitudinal Analysis of a Large Clinic-Based Cohort.Frontiers in pediatrics · 2021Article
- FMRP-Driven Neuropathology in Autistic Spectrum Disorder and Alzheimer's disease: A Losing Game.Frontiers in molecular biosciences · 2021Review
- Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia.Neuroreport · 2020Article
- Transcriptome analysis of rat dorsal hippocampal CA1 after an early life seizure induced by kainic acid.Epilepsy research · 2020Article
- EEG Abnormalities as a Neurophysiological Biomarker of Severity in Autism Spectrum Disorder: A Pilot Cohort Study.Journal of autism and developmental disorders · 2019Article
- Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions.PloS one · 2019Article
- Protein Translation in the Nucleus Accumbens Is Dysregulated during Cocaine Withdrawal and Required for Expression of Incubation of Cocaine Craving.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Implications of thePediatrics · 2017Review
- Superimposing Status Epilepticus on Neuron Subset-Specific PTEN Haploinsufficient and Wild Type Mice Results in Long-term Changes in Behavior.Scientific reports · 2016Article
- Article
- Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure.Neurobiology of disease · 2016Article
- Seizure induced synaptic plasticity alteration in hippocampus is mediated by IL-1β receptor through PI3K/Akt pathway.American journal of translational research · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Outside of Fragile X syndrome (FXS), the role of Fragile-X Mental Retardation Protein (FMRP) in mediating neuropsychological abnormalities is not clear. FMRP, p70-S6 kinase (S6K) and protein phosphatase 2A (PP2A) are thought to cooperate as a dynamic signaling complex. In our prior work, adult rats have enhanced CA1 hippocampal long-term depression (LTD) following an early life seizure (ELS). We now show that mGluR-mediated LTD (mLTD) is specifically enhanced following ELS, similar to FMRP knock-outs. Total FMRP expression is unchanged but S6K is hyperphosphorylated, consistent with S6K overactivation. We postulated that either disruption of the FMRP-S6K-PP2A complex and/or removal of this complex from synapses could explain our findings. Using subcellular fractionation, we were surprised to find that concentrations of FMRP and PP2A were undisturbed in the synaptosomal compartment but reduced in parallel in the cytosolic compartment. Following ELS FMRP phosphorylation was reduced in the cytosolic compartment and increased in the synaptic compartment, in parallel with the compartmentalization of S6K activation. Furthermore, FMRP and PP2A remain bound following ELS. In contrast, the interaction of S6K with FMRP is reduced by ELS. Blockade of PP2A results in enhanced mLTD; this is occluded by ELS. This suggests a critical role for the location and function of the FMRP-S6K-PP2A signaling complex in limiting the amount of mLTD. Specifically, non-synaptic targeting and the function of the complex may influence the "set-point" for regulating mLTD. Consistent with this, striatal-enriched protein tyrosine phosphatase (STEP), an FMRP "target" which regulates mLTD expression, is specifically increased in the synaptosomal compartment following ELS. Further, we provide behavioral data to suggest that FMRP complex dysfunction may underlie altered socialization, a symptom associated and observed in other rodent models of autism, including FXS.
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