ArticleThe Journal of cell biology2015
KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 91 citations in OpenAlex.
- Differential isoform-specific control of KCC2 function in developing and mature cortical neurons.EMBO reports · 2026Article
- Transcriptomics and proteomics of projection neurons in a circuit linking hippocampus with dorsolateral prefrontal cortex in the human brain.bioRxiv : the preprint server for biology · 2026Article
- Acceleration of axonal regeneration by GABA/Gly excitation.Anatomical science international · 2026Review
- Focal cortical dysplasias: modeling pediatric drug-resistant epilepsy using human brain organoids.Frontiers in cellular neuroscience · 2026Review
- Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate KFEBS open bio · 2025Article
- Altered GABAergic signaling and chloride homeostasis in eye movement circuits during late neurodevelopment: implications for Alzheimer's disease therapy.Frontiers in pharmacology · 2025Review
- Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects.Animal cells and systems · 2025Article
- Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.Frontiers in molecular neuroscience · 2024Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- Silencing KCC2 in mouse dorsal hippocampus compromises spatial and contextual memory.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- An isoform-specific function of Cdc42 in regulating mammalian Exo70 during axon formation.Life science alliance · 2023Article
- KFrontiers in cellular neuroscience · 2023Article
- Neural mechanism underlies CYLD modulation of morphology and synaptic function of medium spiny neurons in dorsolateral striatum.Frontiers in molecular neuroscience · 2023Article
- TGF-β2 Regulates Transcription of the KCells · 2022Article
- Gephyrin Interacts with the K-Cl Cotransporter KCC2 to Regulate Its Surface Expression and Function in Cortical Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Chloride imbalance in Fragile X syndrome.Frontiers in neuroscience · 2022Article
- Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons.Frontiers in molecular neuroscience · 2022Article
- Three-Day Continuous Oxytocin Infusion Attenuates Thermal and Mechanical Nociception by Rescuing Neuronal Chloride HomeostasisFrontiers in pharmacology · 2022Article
- Pharmacological intervention in young adolescents rescues synaptic physiology and behavioural deficits in Syngap1Experimental brain research · 2022Article
- Kinesin-1-dependent transport of the βPIX/GIT complex in neuronal cells.BMB reports · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses.
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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.