ArticleProceedings of the National Academy of Sciences of the United States of America2015
Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures.
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 83 papers.
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Who cites it
83 citing papers in PubMed, 124 citations in OpenAlex.
- SPG601-associated modulation of resting-state EEG and improvement in executive function in a fragile X syndrome randomized controlled crossover study.Scientific reports · 2026Trial
- Unraveling in vitro phase separation and aggregation properties of the structured region of FMRP and the impact of Fragile X syndrome-linked mutations.The FEBS journal · 2026Article
- FMR1 KH0-KH1 domains coordinate mExperimental cell research · 2025Article
- Neuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators.Science advances · 2025Article
- Convergent depression of activity-dependent bulk endocytosis in rodent models of autism spectrum disorder.Molecular autism · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Age-dependent impairment of dopamine D1 receptor signalling in mouse striatum byBrain communications · 2025Article
- Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- FMR1 genetically interacts with DISC1 to regulate glutamatergic synaptogenesis.Schizophrenia (Heidelberg, Germany) · 2024Article
- Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment.Biomolecules · 2024Article
- Large conductance voltage-and calcium-activated KFrontiers in pharmacology · 2024Review
- 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
- Deregulation of ER-mitochondria contact formation and mitochondrial calcium homeostasis mediated by VDAC in fragile X syndrome.Developmental cell · 2023Article
- Axonal and presynaptic FMRP: Localization, signal, and functional implications.Hearing research · 2023Review
- Mouse models of fragile X-related disorders.Disease models & mechanisms · 2023Review
- Folding Mechanism and Aggregation Propensity of the KH0 Domain of FMRP and Its R138Q Pathological Variant.International journal of molecular sciences · 2022Article
- FMRP regulates GABACell reports · 2022Article
- Large-conductance calcium-activated potassium channel haploinsufficiency leads to sensory deficits in the visual system: a case report.Journal of medical case reports · 2022Article
- Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice.Brain : a journal of neurology · 2022Article
- FMRP Sustains Presynaptic Function via Control of Activity-Dependent Bulk Endocytosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Fragile X syndrome (FXS) results in intellectual disability (ID) most often caused by silencing of the fragile X mental retardation 1 (FMR1) gene. The resulting absence of fragile X mental retardation protein 1 (FMRP) leads to both pre- and postsynaptic defects, yet whether the pre- and postsynaptic functions of FMRP are independent and have distinct roles in FXS neuropathology remain poorly understood. Here, we demonstrate an independent presynaptic function for FMRP through the study of an ID patient with an FMR1 missense mutation. This mutation, c.413G > A (R138Q), preserves FMRP's canonical functions in RNA binding and translational regulation, which are traditionally associated with postsynaptic compartments. However, neuronally driven expression of the mutant FMRP is unable to rescue structural defects at the neuromuscular junction in fragile x mental retardation 1 (dfmr1)-deficient Drosophila, suggesting a presynaptic-specific impairment. Furthermore, mutant FMRP loses the ability to rescue presynaptic action potential (AP) broadening in Fmr1 KO mice. The R138Q mutation also disrupts FMRP's interaction with the large-conductance calcium-activated potassium (BK) channels that modulate AP width. These results reveal a presynaptic- and translation-independent function of FMRP that is linked to a specific subset of FXS phenotypes.
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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.