Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1
Open accessAbstract
Dysfunction of the neuronal RNA binding protein RBFOX1 has been linked to epilepsy and autism spectrum disorders. Rbfox1 loss in mice leads to neuronal hyper-excitability and seizures, but the physiological basis for this is unknown. We identify the vSNARE protein Vamp1 as a major Rbfox1 target. Vamp1 is strongly downregulated in Rbfox1 Nes-cKO mice due to loss of 3' UTR binding by RBFOX1. Cytoplasmic Rbfox1 stimulates Vamp1 expression in part by blocking microRNA-9. We find that Vamp1 is specifically expressed in inhibitory neurons, and that both Vamp1 knockdown and Rbfox1 loss lead to decreased inhibitory synaptic transmission and E/I imbalance. Re-expression of Vamp1 selectively within interneurons rescues the electrophysiological changes in the Rbfox1 cKO, indicating that Vamp1 loss is a major contributor to the Rbfox1 Nes-cKO phenotype. The regulation of interneuron-specific Vamp1 by Rbfox1 provides a paradigm for broadly expressed RNA-binding proteins performing specialized functions in defined neuronal subtypes.
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Mouse experiments indicate RBFOX1 has distinct nuclear and cytoplasmic isoforms with differing functions.
“Experiments in mouse indicate that RBFOX1 has distinct nuclear and cytoplasmic isoforms with differing functions, the nuclear isoform primarily regulating pre-mRNA alternative splicing, and the cytoplasmic isoform binding to the 3’ UTR to stabilize target transcripts involved in regulation of neuronal excitability (28, 32, 58, 60).”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [58]
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- Bill BR Lowe JK Dybuncio CT Fogel BL 2013 Orchestration of neurodevelop-mental programs by RBFOX1: implications for autism spectrum disorder Int Rev Neurobiol 113 251 267 24290388 PMC4318517
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- Authors
- Vuong, C. K., Wei, W., Lee, J.-A., Lin, C.-H., Damianov, A., de la Torre-Ubieta, L., Halabi, R., Otis, K. O., Martin, K. C., O’Dell, T. J., & Black, D. L.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Black, Douglas L.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 98
- Issue
- 1
- Pages
- 127-141.e7
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5890944
- OpenAlex
- W2796191989
- Cited by
- 102
- References
- 86
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 14 · 2023: 11 · 2022: 20 · 2021: 9 · 2020: 13 · 2019: 8 · 2018: 4
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (T32 GM007185, F31 NS093923, R21 MH101684, R01 MH060919, R01 GM114463)
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- RBFOX1, VAMP1, synaptic transmission, inhibitory interneurons, 3' UTR regulation, miR-9, neuronal excitability, epilepsy, autism spectrum disorder
- MeSH terms
- RNA Splicing Factors, Animals, Cells, Cultured, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Neural Inhibition, Synaptic Transmission, Neurons, Mice, Knockout, SNARE Proteins, Vesicle-Associated Membrane Protein 1, Mice, Mice, 129 Strain
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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