Lateral diffusion of NKCC1 contributes to neuronal chloride homeostasis and is rapidly regulated by the WNK signaling pathway
Come, E.; Blachier, S.; Gouhier, J.; Russeau, M.; LEVI, S.
Show abstract
An upregulation of the Na+-K+-2Cl- co-transporter NKCC1, the main chloride importer in mature neurons, can lead to depolarizing/excitatory responses mediated by GABAA receptors and thus to hyperactivity. Understanding the regulatory mechanisms of NKCC1 would help prevent intra-neuronal chloride accumulation that occurs in pathologies with defective inhibition. The cellular and molecular regulatory mechanisms of NKCC1 are poorly understood. Here, we report in mature hippocampal neurons that GABAergic activity controls the membrane diffusion and clustering of NKCC1 via the chloride-sensitive WNK1 kinase and the downstream SPAK kinase that directly phosphorylates NKCC1 on key threonine residues. At rest, this signaling pathway has little effect on intracellular Cl- concentration but it participates to the elevation of intraneuronal Cl- concentration in hyperactivity condition associated with an up-regulation of NKCC1. The fact that the chloride exporter KCC2 is also regulated in mature neurons by the WNK1 pathway indicates that this pathway will be a target of choice in the pathology.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Glycine receptor α3K governs mobility and conductance of L/K splice variant heteropentamers 95%
- Restricting α-Synuclein Transport into Mitochondria by Inhibition of α-Synuclein-VDAC Complexation as a Potential Therapeutic Target for Parkinson's Disease Treatment 94%
- Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor 93%
Similar papers in this journal
- Spinal cord synaptic plasticity by GlyRβ release from receptor fields and syndapin-dependent uptake 94%
- Extrasynaptic NMDA receptors bidirectionally modulate intrinsic excitability of inhibitory neurons 94%
- Synaptotagmin 9 modulates spontaneous neurotransmitter release in striatal neurons by regulating substance P secretion 94%
Similar papers in this journal
- Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter 94%
- Abnormal AMPAR-mediated synaptic plasticity, cognitive and autistic-like behaviors in a missense Fmr1 mutant mouse model of Fragile X syndrome 93%
- Functional recruitment of dynamin requires multimeric interactions for efficient endocytosis 93%
Similar papers in this journal
- Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability 94%
- Restoring Glutamate receptosome dynamics at synapses rescues Autism-like deficits in Shank3-deficient mice. 94%
- Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsense Shank3 mutation 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.