ArticleProceedings of the National Academy of Sciences of the United States of America2011
The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 134 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- Differential isoform-specific control of KCC2 function in developing and mature cortical neurons.EMBO reports · 2026Article
- Molecular pathways underlying amyloid precursor protein-mediated regulation of adult-born neurons.Neural regeneration research · 2026Article
- Learning Dynamics in Biophysical Spiking Network Models Are Shaped by KCC2/NKCC1 Cotransporter Stoichiometry.The European journal of neuroscience · 2026Article
- Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the perinatal cortex.Nature communications · 2025Article
- Altered GABAergic signaling and chloride homeostasis in eye movement circuits during late neurodevelopment: implications for Alzheimer's disease therapy.Frontiers in pharmacology · 2025Review
- ClScience advances · 2024Article
- Unraveling the socio-cognitive consequences of KCC2 disruption in zebrafish: implications for neurodevelopmental disorders and therapeutic interventions.Frontiers in molecular neuroscience · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- NKCC1 and KCC2 Chloride Transporters Have Different Membrane Dynamics on the Surface of Hippocampal Neurons.Cells · 2023Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- Delaying the GABA Shift Indirectly Affects Membrane Properties in the Developing Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Silencing KCC2 in mouse dorsal hippocampus compromises spatial and contextual memory.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- KCC2 downregulation after sciatic nerve injury enhances motor function recovery.Scientific reports · 2023Article
- Layer-specific changes of KCC2 and NKCC1 in the mouse dentate gyrus after entorhinal denervation.Frontiers in molecular neuroscience · 2023Article
- Gamma frequency light flicker regulates amyloid precursor protein trafficking for reducing β-amyloid load in Alzheimer's disease model.Aging cell · 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
- Shared mechanisms of neural circuit disruption in tuberous sclerosis across lifespan: Bridging neurodevelopmental and neurodegenerative pathology.Frontiers in genetics · 2022Review
- Chloride imbalance in Fragile X syndrome.Frontiers in neuroscience · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The K-Cl cotransporter KCC2 plays an essential role in neuronal chloride homeostasis, and thereby influences the efficacy and polarity of GABA signaling. Although KCC2 is expressed throughout the somatodendritic membrane, it is remarkably enriched in dendritic spines, which host most glutamatergic synapses in cortical neurons. KCC2 has been shown to influence spine morphogenesis and functional maturation in developing neurons, but its function in mature dendritic spines remains unknown. Here, we report that suppressing KCC2 expression decreases the efficacy of excitatory synapses in mature hippocampal neurons. This effect correlates with a reduced postsynaptic aggregation of GluR1-containing AMPA receptors and is mimicked by a dominant negative mutant of KCC2 interaction with cytoskeleton but not by pharmacological suppression of KCC2 function. Single-particle tracking experiments reveal that suppressing KCC2 increases lateral diffusion of the mobile fraction of AMPA receptor subunit GluR1 in spines but not in adjacent dendritic shafts. Increased diffusion was also observed for transmembrane but not membrane-anchored recombinant neuronal cell adhesion molecules. We suggest that KCC2, likely through interactions with the actin cytoskeleton, hinders transmembrane protein diffusion, and thereby contributes to their confinement within dendritic spines.
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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.