ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Upregulation of the neuron-specific K+/Cl- cotransporter expression by transcription factor early growth response 4.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 76 citations in OpenAlex.
- Subtype- and Layer-Specific Developmental Gradients of Postnatal GABAergic Neurons in the Rodent Barrel Cortex.Developmental neuroscience · 2025Article
- Small-molecule agonist AdipoRon alleviates diabetic retinopathy through the AdipoR1/AMPK/EGR4 pathway.Journal of translational medicine · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- SLC12A5 as a novel potential biomarker of glioblastoma multiforme.Molecular biology reports · 2023Article
- Impaired synaptic plasticity in an animal model of autism exhibiting early hippocampal GABAergic-BDNF/TrkB signaling alterations.iScience · 2023Article
- TGF-β2 Regulates Transcription of the KCells · 2022Article
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- NKCC1 Deficiency in Forming Hippocampal Circuits Triggers Neurodevelopmental Disorder: Role of BDNF-TrkB Signalling.Brain sciences · 2022Review
- 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
- The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology.Frontiers in physiology · 2022Review
- The Alteration of Chloride Homeostasis/GABAergic Signaling in Brain Disorders: Could Oxidative Stress Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
- The DNA repair protein ATM as a target in autism spectrum disorder.JCI insight · 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
- Isolation and Characterization of Multi-Protein Complexes Enriched in the K-Cl Co-transporter 2 From Brain Plasma Membranes.Frontiers in molecular neuroscience · 2020Article
- Developmental Regulation of KCC2 Phosphorylation Has Long-Term Impacts on Cognitive Function.Frontiers in molecular neuroscience · 2019Article
- The primate-specific peptide Y-P30 regulates morphological maturation of neocortical dendritic spines.PloS one · 2019Article
- Reciprocal Regulation of KCC2 Trafficking and Synaptic Activity.Frontiers in cellular neuroscience · 2019Review
- Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal KBioMed research international · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of the neuron-specific K+/Cl- cotransporter (KCC2) is restricted to the CNS and is strongly upregulated during neuronal maturation, yielding a low intracellular chloride concentration that is required for fast synaptic inhibition in adult neurons. To elucidate the mechanisms of KCC2 gene regulation, we analyzed the KCC2 (alias Slc12a5) promoter and proximal intron-1 regions and revealed 10 candidate transcription factor binding sites that are highly conserved in mammalian KCC2 genes. Here we focus on one of these factors, early growth response 4 (Egr4), which shows a similar developmental upregulation in CNS neurons as KCC2. KCC2 luciferase reporter constructs containing the Egr4 site (Egr4(KCC2)) were strongly induced by Egr4 overexpression in neuro-2a neuroblastoma cells and in cultured neurons. Egr4-mediated induction was decreased significantly by point-mutating the Egr4(KCC2). Insertion of Egr4(KCC2) into the KCC2 basal promoter in the endogenous reverse, but not in the opposite, orientation reestablished Egr4-mediated induction. Electrophoretic mobility shift assay confirmed specific Egr4 binding to Egr4(KCC2). Interference RNA-mediated knock-down of Egr4 and a dominant-negative isoform of Egr4 significantly inhibited KCC2 reporter induction and endogenous KCC2 expression in cultured neurons. Together, the results indicate an important role for Egr4 in the developmental upregulation of KCC2 gene expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.