ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Stabilization of GABA(A) receptors at endocytic zones is mediated by an AP2 binding motif within the GABA(A) receptor β3 subunit.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 63 citations in OpenAlex.
- GABASynapse (New York, N.Y.) · 2026Review
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- AExperimental and therapeutic medicine · 2025Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner.Communications biology · 2024Article
- TRPM2 and CaMKII Signaling Drives Excessive GABAergic Synaptic Inhibition Following Ischemia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Research advances in huntingtin-associated protein 1 and its application prospects in diseases.Frontiers in neuroscience · 2024Review
- Article
- NKCC1 and KCC2 Chloride Transporters Have Different Membrane Dynamics on the Surface of Hippocampal Neurons.Cells · 2023Article
- Conformational state-dependent regulation of GABAiScience · 2022Article
- Trophic factor BDNF inhibits GABAergic signaling by facilitating dendritic enrichment of SUMO E3 ligase PIAS3 and altering gephyrin scaffold.The Journal of biological chemistry · 2022Article
- Human ARHGEF9 intellectual disability syndrome is phenocopied by a mutation that disrupts collybistin binding to the GABAMolecular psychiatry · 2022Article
- Stepwise disassembly of GABAergic synapses during pathogenic excitotoxicity.Cell reports · 2021Article
- Genome-wide DNA methylation alteration in prenatally stressed Brahman heifer calves with the advancement of age.Epigenetics · 2021Article
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- The Therapeutic Potential of Neuronal K-Cl Co-Transporter KCC2 in Huntington's Disease and Its Comorbidities.International journal of molecular sciences · 2020Review
- Proteomics Reveals the Potential Protective Mechanism of Hydrogen Sulfide on Retinal Ganglion Cells in an Ischemia/Reperfusion Injury Animal Model.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Endocytosis in the adaptation to cellular stress.Cell stress · 2020Review
- AP-2 reduces amyloidogenesis by promoting BACE1 trafficking and degradation in neurons.EMBO reports · 2020Article
- DISC1 Regulates Mitochondrial Trafficking in a Miro1-GTP-Dependent Manner.Frontiers in cell and developmental biology · 2020Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The strength of synaptic inhibition can be controlled by the stability and endocytosis of surface and synaptic GABA(A) receptors (GABA(A)Rs), but the surface receptor dynamics that underpin GABA(A)R recruitment to dendritic endocytic zones (EZs) have not been investigated. Stabilization of GABA(A)Rs at EZs is likely to be regulated by receptor interactions with the clathrin-adaptor AP2, but the molecular determinants of these associations remain poorly understood. Moreover, although surface GABA(A)R downmodulation plays a key role in pathological disinhibition in conditions such as ischemia and epilepsy, whether this occurs in an AP2-dependent manner also remains unclear. Here we report the characterization of a novel motif containing three arginine residues (405RRR407) within the GABA(A)R β3-subunit intracellular domain (ICD), responsible for the interaction with AP2 and GABA(A)R internalization. When this motif is disrupted, binding to AP2 is abolished in vitro and in rat brain. Using single-particle tracking, we reveal that surface β3-subunit-containing GABA(A)Rs exhibit highly confined behavior at EZs, which is dependent on AP2 interactions via this motif. Reduced stabilization of mutant GABA(A)Rs at EZs correlates with their reduced endocytosis and increased steady-state levels at synapses. By imaging wild-type or mutant super-ecliptic pHluorin-tagged GABA(A)Rs in neurons, we also show that, under conditions of oxygen-glucose deprivation to mimic cerebral ischemia, GABA(A)Rs are depleted from synapses in dendrites, depending on the 405RRR407 motif. Thus, AP2 binding to an RRR motif in the GABA(A)R β3-subunit ICD regulates GABA(A)R residency time at EZs, steady-state synaptic receptor levels, and pathological loss of GABA(A)Rs from synapses during simulated ischemia.
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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.