ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Novel repression of Kcc2 transcription by REST-RE-1 controls developmental switch in neuronal chloride.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 85 citations in OpenAlex.
- Phosphorylation by CaMKIV regulates the transcriptional repressor activity and half-life of REST/NRSF.Science advances · 2026Article
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.Acta pharmacologica Sinica · 2024Review
- Abnormality in GABAergic postsynaptic transmission associated with anxiety inIBRO neuroscience reports · 2024Article
- SLC12A5 as a novel potential biomarker of glioblastoma multiforme.Molecular biology reports · 2023Article
- Inhibitory Synaptic Influences on Developmental Motor Disorders.International journal of molecular sciences · 2023Review
- Conditional knockout of REST/NRSF in excitatory neurons reduces seizure susceptibility to chemical kindling.Frontiers in cellular neuroscience · 2023Article
- TGF-β2 Regulates Transcription of the KCells · 2022Article
- How Staying Negative Is Good for the (Adult) Brain: Maintaining Chloride Homeostasis and the GABA-Shift in Neurological Disorders.Frontiers in molecular neuroscience · 2022Review
- Long March Toward Safe and Effective Analgesia by Enhancing Gene Expression ofFrontiers in molecular neuroscience · 2022Review
- Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission.Nature communications · 2021Article
- The functions of repressor element 1-silencing transcription factor in models of epileptogenesis and post-ischemia.Metabolic brain disease · 2021Review
- Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Establishment of Novel Protein Interaction Assays between Sin3 and REST Using Surface Plasmon Resonance and Time-Resolved Fluorescence Energy Transfer.International journal of molecular sciences · 2021Article
- Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington's Disease.Frontiers in cellular neuroscience · 2021Review
- The Therapeutic Potential of Neuronal K-Cl Co-Transporter KCC2 in Huntington's Disease and Its Comorbidities.International journal of molecular sciences · 2020Review
- Environmental regulation of the chloride transporter KCC2: switching inflammation off to switch the GABA on?Translational psychiatry · 2020Review
- Transcriptional regulation of adult neural stem/progenitor cells: tales from the subventricular zone.Neural regeneration research · 2020Review
- Article
- The paradox of opposite directions of gene expressions in MCI and AD suggests possible therapy to prevent progression of MCI to AD.Alzheimer's & dementia (New York, N. Y.) · 2020Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Transcriptional upregulation of Kcc2b, the gene variant encoding the major isoform of the KCC2 chloride transporter, underlies a rapid perinatal decrease in intraneuronal chloride concentration (chloride shift), which is necessary for GABA to act inhibitory. Here we identify a novel repressor element-1 (RE-1) site in the 5' regulatory region of Kcc2b. In primary cortical neurons, which recapitulate the chloride shift in culture, the novel upstream RE-1 together with a known intronic RE-1 site function in concerted interaction to suppress Kcc2b transcription. With critical relevance for the chloride shift, only in the presence of the dual RE-1 site could inhibition of REST upregulate Kcc2b transcription. For this, we confirmed increased KCC2 protein expression and decreased intraneuronal chloride. Kcc2b developmental upregulation was potentiated by BDNF application, which was fully dependent on the presence of dual RE-1. In addition, the developmental chloride shift and GABA switch, from excitatory to inhibitory action, was accelerated by REST inhibition and slowed by REST overexpression. These results identify the REST-dual RE-1 interaction as a novel mechanism of transcriptional Kcc2b upregulation that significantly contributes to the ontogenetic shift in chloride concentration and GABA action in cortical neurons, which is fundamental for brain function in health and disease. Thus, we present here a new logic for the perinatal chloride shift, which is critical for establishment of GABAergic cortical inhibitory neurotransmission.
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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.