ArticleThe Journal of biological chemistry2012
Taurine inhibits K+-Cl- cotransporter KCC2 to regulate embryonic Cl- homeostasis via with-no-lysine (WNK) protein kinase signaling pathway.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 97 citations in OpenAlex.
- KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.Frontiers in molecular neuroscience · 2026Article
- Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation-Chloride Cotransporters in Rat Cortical Neurons.International journal of molecular sciences · 2024Article
- Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.Frontiers in molecular neuroscience · 2024Article
- Inhibition of WNK Kinases in NK Cells Disrupts Cellular Osmoregulation and Control of Tumor Metastasis.Journal of innate immunity · 2024Article
- Serine 937 phosphorylation enhances KCC2 activity and strengthens synaptic inhibition.Scientific reports · 2023Article
- Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023Review
- Maternal taurine as a modulator of ClFrontiers in cellular neuroscience · 2023Review
- KFrontiers in cellular neuroscience · 2023Article
- Effects of Taurine Depletion on Body Weight and Mouse Behavior during Development.Metabolites · 2022Article
- Inhibiting with-no-lysine kinases enhances K+/Cl- cotransporter 2 activity and limits status epilepticus.Brain : a journal of neurology · 2022Article
- Taurine depletion during fetal and postnatal development blunts firing responses of neocortical layer II/III pyramidal neurons.Frontiers in molecular neuroscience · 2022Article
- WNK3 kinase maintains neuronal excitability by reducing inwardly rectifying KFrontiers in molecular neuroscience · 2022Article
- NKCC1 and KCC2: Structural insights into phospho-regulation.Frontiers in molecular neuroscience · 2022Review
- Arbitrary CaFrontiers in pharmacology · 2022Article
- The Alteration of Chloride Homeostasis/GABAergic Signaling in Brain Disorders: Could Oxidative Stress Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
- Chloride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis.Nature communications · 2021Article
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- When Are Depolarizing GABAergic Responses Excitatory?Frontiers in molecular neuroscience · 2021Review
- Article
- Leptin down-regulates KCC2 activity and controls chloride homeostasis in the neonatal rat hippocampus.Molecular brain · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA inhibits mature neurons and conversely excites immature neurons due to lower K(+)-Cl(-) cotransporter 2 (KCC2) expression. We observed that ectopically expressed KCC2 in embryonic cerebral cortices was not active; however, KCC2 functioned in newborns. In vitro studies revealed that taurine increased KCC2 inactivation in a phosphorylation-dependent manner. When Thr-906 and Thr-1007 residues in KCC2 were substituted with Ala (KCC2T906A/T1007A), KCC2 activity was facilitated, and the inhibitory effect of taurine was not observed. Exogenous taurine activated the with-no-lysine protein kinase 1 (WNK1) and downstream STE20/SPS1-related proline/alanine-rich kinase (SPAK)/oxidative stress response 1 (OSR1), and overexpression of active WNK1 resulted in KCC2 inhibition in the absence of taurine. Phosphorylation of SPAK was consistently higher in embryonic brains compared with that of neonatal brains and down-regulated by a taurine transporter inhibitor in vivo. Furthermore, cerebral radial migration was perturbed by a taurine-insensitive form of KCC2, KCC2T906A/T1007A, which may be regulated by WNK-SPAK/OSR1 signaling. Thus, taurine and WNK-SPAK/OSR1 signaling may contribute to embryonic neuronal Cl(-) homeostasis, which is required for normal brain development.
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