ArticleThe Journal of biological chemistry2012
γ-Aminobutyric acid type A (GABAA) receptor α subunits play a direct role in synaptic versus extrasynaptic targeting.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Unveiling GABA and Serotonin Interactions During Neurodevelopment to Re-Open Adult Critical Periods for Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- Noise-induced hearing loss alters potassium-chloride cotransporter KCC2 and GABA inhibition in the auditory centers.Scientific reports · 2024Article
- Noise-Induced Hearing Loss Alters Potassium-Chloride CoTransporter KCC2 and GABA Inhibition in the auditory centers.Research square · 2023Article
- Structure, function, and pathology of Neurexin-3.Genes & diseases · 2023Review
- Neurodevelopmental Toxicity of Emamectin Benzoate to the Early Life Stage of Zebrafish Larvae (International journal of molecular sciences · 2023Article
- Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.Cellular and molecular neurobiology · 2022Article
- Hyperammonemia Enhances GABAergic Neurotransmission in Hippocampus: Underlying Mechanisms and Modulation by Extracellular cGMP.Molecular neurobiology · 2022Article
- Enhancement of parvalbumin interneuron-mediated neurotransmission in the retrosplenial cortex of adolescent mice following third trimester-equivalent ethanol exposure.Scientific reports · 2021Article
- Regulation of GABAInternational journal of molecular sciences · 2020Review
- Neurotransmitter changes after traumatic brain injury: an update for new treatment strategies.Molecular psychiatry · 2019Review
- Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.Behavioural brain research · 2019Article
- Presynaptic GABAA Receptors Modulate Thalamocortical Inputs in Layer 4 of Rat V1.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Identification of transthyretin as a novel interacting partner for the δ subunit of GABAA receptors.PloS one · 2019Article
- Chemogenetic Isolation Reveals Synaptic Contribution of δ GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Comparison of electrophysiological properties of two types of pre-sympathetic neurons intermingled in the hypothalamic paraventricular nucleus.Journal of veterinary science · 2018Article
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- SAHA (Vorinostat) Corrects Inhibitory Synaptic Deficits Caused by Missense Epilepsy Mutations to the GABAFrontiers in molecular neuroscience · 2018Article
- PR-independent neurosteroid regulation of α2-GABA-A receptors in the hippocampus subfields.Brain research · 2017Article
- γ1-Containing GABA-A Receptors Cluster at Synapses Where they Mediate Slower Synaptic Currents than γ2-Containing GABA-A Receptors.Frontiers in molecular neuroscience · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
GABA(A) receptors (GABA(A)-Rs) are localized at both synaptic and extrasynaptic sites, mediating phasic and tonic inhibition, respectively. Previous studies suggest an important role of γ2 and δ subunits in synaptic versus extrasynaptic targeting of GABA(A)-Rs. Here, we demonstrate differential function of α2 and α6 subunits in guiding the localization of GABA(A)-Rs. To study the targeting of specific subtypes of GABA(A)-Rs, we used a molecularly engineered GABAergic synapse model to precisely control the GABA(A)-R subunit composition. We found that in neuron-HEK cell heterosynapses, GABAergic events mediated by α2β3γ2 receptors were very fast (rise time ∼2 ms), whereas events mediated by α6β3δ receptors were very slow (rise time ∼20 ms). Such an order of magnitude difference in rise time could not be attributed to the minute differences in receptor kinetics. Interestingly, synaptic events mediated by α6β3 or α6β3γ2 receptors were significantly slower than those mediated by α2β3 or α2β3γ2 receptors, suggesting a differential role of α subunit in receptor targeting. This was confirmed by differential targeting of the same δ-γ2 chimeric subunits to synaptic or extrasynaptic sites, depending on whether it was co-assembled with the α2 or α6 subunit. In addition, insertion of a gephyrin-binding site into the intracellular domain of α6 and δ subunits brought α6β3δ receptors closer to synaptic sites. Therefore, the α subunits, together with the γ2 and δ subunits, play a critical role in governing synaptic versus extrasynaptic targeting of GABA(A)-Rs, possibly through differential interactions with gephyrin.
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Registered trials
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.