ArticleFrontiers in cellular neuroscience2015
Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 43 citations in OpenAlex.
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
- Genome-wide transcriptome profiling and development of age prediction models in the human brain.Aging · 2024Article
- Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.Nature communications · 2023Article
- Sex-specific differences in KCC2 localisation and inhibitory synaptic transmission in the rat hippocampus.Scientific reports · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Conditional knockout of Tsc1 in RORγt-expressing cells induces brain damage and early death in mice.Journal of neuroinflammation · 2021Article
- Kainate Receptor Activation Shapes Short-Term Synaptic Plasticity by Controlling Receptor Lateral Mobility at Glutamatergic Synapses.Cell reports · 2020Article
- Ionotropic and metabotropic kainate receptor signalling regulates ClThe Journal of physiology · 2019Article
- KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
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- Neto Auxiliary Subunits Regulate Interneuron Somatodendritic and Presynaptic Kainate Receptors to Control Network Inhibition.Cell reports · 2017Article
- A kainate receptor subunit promotes the recycling of the neuron-specific KThe Journal of biological chemistry · 2017Article
- Neto2 Assembles with Kainate Receptors in DRG Neurons during Development and Modulates Neurite Outgrowth in Adult Sensory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- The membrane trafficking and functionality of the K+-Cl- co-transporter KCC2 is regulated by TGF-β2.Journal of cell science · 2016Article
- Review
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neto2 is a transmembrane protein that interacts with the neuron-specific K(+)-Cl(-) cotransporter (KCC2) in the central nervous system (CNS). Efficient KCC2 transport is essential for setting the neuronal Cl(-) gradient, which is required for fast GABAergic inhibition. Neto2 is required to maintain the normal abundance of KCC2 in neurons, and increases KCC2 function by binding to the active oligomeric form of this cotransporter. In the present study, we characterized GABAergic inhibition and KCC2-mediated neuronal chloride homeostasis in pyramidal neurons from adult hippocampal slices. Using gramicidin perforated patch clamp recordings we found that the reversal potential for GABA (EGABA) was significantly depolarized. We also observed that surface levels of KCC2 and phosphorylation of KCC2 serine 940 (Ser940) were reduced in Neto2(-/-) neurons compared to wild-type controls. To examine GABAergic inhibition we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) and found that Neto2(-/-) neurons had significant reductions in both their amplitude and frequency. Based on the critical role of Neto2 in regulating GABAergic inhibition we rationalized that Neto2-null mice would be prone to seizure activity. We found that Neto2-null mice demonstrated a decrease in the latency to pentylenetetrazole (PTZ)-induced seizures and an increase in seizure severity.
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