ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Disruption of GpI mGluR-Dependent Cav2.3 Translation in a Mouse Model of Fragile X Syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability.Nature communications · 2023Article
- From circuits to behavior: Amygdala dysfunction in fragile X syndrome.Frontiers in integrative neuroscience · 2023Review
- The glutamate metabotropic receptor 5 (GRM5) gene is associated with beef cattle home range and movement tortuosity.Journal of animal science and biotechnology · 2022Article
- Role of Group I Metabotropic Glutamate Receptors in Spike Timing-Dependent Plasticity.International journal of molecular sciences · 2022Article
- Mechanisms Driving the Emergence of Neuronal Hyperexcitability in Fragile X Syndrome.International journal of molecular sciences · 2022Review
- R-type voltage-gated CaCell reports · 2022Article
- Targeting N-type calcium channels in young-onset of some neurological diseases.Frontiers in cell and developmental biology · 2022Review
- ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research.Molecular psychiatry · 2021Article
- Channelopathies in fragile X syndrome.Nature reviews. Neuroscience · 2021Review
- FMRP regulates presynaptic localization of neuronal voltage gated calcium channels.Neurobiology of disease · 2020Article
- Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules.Biomolecules · 2020Review
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Authors and funding
7 authors at 1 institution in 4 countries.
Funding
Abstract
Fragile X syndrome (FXS) is an inherited intellectual impairment that results from the loss of fragile X mental retardation protein (FMRP), an mRNA binding protein that regulates mRNA translation at synapses. The absence of FMRP leads to neuronal and circuit-level hyperexcitability that is thought to arise from the aberrant expression and activity of voltage-gated ion channels, although the identification and characterization of these ion channels have been limited. Here, we show that FMRP binds the mRNA of the R-type voltage-gated calcium channel Cav2.3 in mouse brain synaptoneurosomes and represses Cav2.3 translation under basal conditions. Consequently, in hippocampal neurons from male and female FMRP KO mice, we find enhanced Cav2.3 protein expression by western blotting and abnormally large R currents in whole-cell voltage-clamp recordings. In agreement with previous studies showing that FMRP couples Group I metabotropic glutamate receptor (GpI mGluR) signaling to protein translation, we find that GpI mGluR stimulation results in increased Cav2.3 translation and R current in hippocampal neurons which is disrupted in FMRP KO mice. Thus, FMRP serves as a key translational regulator of Cav2.3 expression under basal conditions and in response to GpI mGluR stimulation. Loss of regulated Cav2.3 expression could underlie the neuronal hyperactivity and aberrant calcium spiking in FMRP KO mice and contribute to FXS, potentially serving as a novel target for future therapeutic strategies.
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