ArticleMolecular brain2013
An unexpected role of neuroligin-2 in regulating KCC2 and GABA functional switch.
Article in Molecular brain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Baseline Dynamics and Sleep Loss-Driven Changes of Electrocorticographic Aperiodic Properties Are Altered in Mice Lacking Neuroligin-2.The European journal of neuroscience · 2026Article
- Heterogeneous subpopulations of GABAiScience · 2024Article
- Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice.Molecular autism · 2024Article
- European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Neurological Anomalies: Geospatiotemporal and Causal Inferential Study.International journal of environmental research and public health · 2022Article
- Article
- The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms.Frontiers in synaptic neuroscience · 2022Review
- Levetiracetam and N-Cadherin Antibody Alleviate Brain Pathology Without Reducing Early Epilepsy Development After Focal Non-convulsive Status Epilepticus in Rats.Frontiers in neurology · 2021Article
- GABAergic System Dysfunction in Autism Spectrum Disorders.Frontiers in cell and developmental biology · 2021Review
- Dysregulation of GABAergic Signaling in Neurodevelomental Disorders: Targeting Cation-Chloride Co-transporters to Re-establish a Proper E/I Balance.Frontiers in cellular neuroscience · 2021Review
- Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons.Scientific reports · 2020Article
- The functional microscopic neuroanatomy of the human subthalamic nucleus.Brain structure & function · 2019Article
- Understanding intellectual disability and autism spectrum disorders from common mouse models: synapses to behaviour.Open biology · 2019Review
- Identification of transthyretin as a novel interacting partner for the δ subunit of GABAA receptors.PloS one · 2019Article
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- The membrane trafficking and functionality of the K+-Cl- co-transporter KCC2 is regulated by TGF-β2.Journal of cell science · 2016Article
- NPY+-, but not PV+- GABAergic neurons mediated long-range inhibition from infra- to prelimbic cortex.Translational psychiatry · 2016Article
- KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Acute TrkB inhibition rescues phenobarbital-resistant seizures in a mouse model of neonatal ischemia.The European journal of neuroscience · 2015Article
- Developmental changes in synaptic distribution in arcuate nucleus neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Proteomics: in pursuit of effective traumatic brain injury therapeutics.Expert review of proteomics · 2015Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGABAA receptors are ligand-gated Cl- channels, and the intracellular Cl- concentration governs whether GABA function is excitatory or inhibitory. During early brain development, GABA undergoes functional switch from excitation to inhibition: GABA depolarizes immature neurons but hyperpolarizes mature neurons due to a developmental decrease of intracellular Cl- concentration. This GABA functional switch is mainly mediated by the up-regulation of KCC2, a potassium-chloride cotransporter that pumps Cl- outside neurons. However, the upstream factor that regulates KCC2 expression is unclear.
resultsWe report here that KCC2 is unexpectedly regulated by neuroligin-2 (NL2), a cell adhesion molecule specifically localized at GABAergic synapses. The expression of NL2 precedes that of KCC2 in early postnatal development. Upon knockdown of NL2, the expression level of KCC2 is significantly decreased, and GABA functional switch is significantly delayed during early development. Overexpression of shRNA-proof NL2 rescues both KCC2 reduction and delayed GABA functional switch induced by NL2 shRNAs. Moreover, NL2 appears to be required to maintain GABA inhibitory function even in mature neurons, because knockdown NL2 reverses GABA action to excitatory. Gramicidin-perforated patch clamp recordings confirm that NL2 directly regulates the GABA equilibrium potential. We further demonstrate that knockdown of NL2 decreases dendritic spines through down-regulating KCC2.
conclusionsOur data suggest that in addition to its conventional role as a cell adhesion molecule to regulate GABAergic synaptogenesis, NL2 also regulates KCC2 to modulate GABA functional switch and even glutamatergic synapses. Therefore, NL2 may serve as a master regulator in balancing excitation and inhibition in the brain.
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