ArticleThe Journal of biological chemistry2013
Agonist-dependent endocytosis of γ-aminobutyric acid type A (GABAA) receptors revealed by a γ2(R43Q) epilepsy mutation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.Journal of translational medicine · 2024Review
- Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine.Patterns (New York, N.Y.) · 2023Review
- Article
- Clptm1, a new target in suppressing epileptic seizure by regulating GABAThe Kaohsiung journal of medical sciences · 2023Article
- Synthesis of Phthaladyn-29 and Naphthalimide-10, GTP Site Directed Dynamin GTPase Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment.International journal of molecular sciences · 2020Review
- Diazepam Accelerates GABAFrontiers in cellular neuroscience · 2019Article
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- Genetic and Molecular Regulation of Extrasynaptic GABA-A Receptors in the Brain: Therapeutic Insights for Epilepsy.The Journal of pharmacology and experimental therapeutics · 2018Review
- SAHA (Vorinostat) Corrects Inhibitory Synaptic Deficits Caused by Missense Epilepsy Mutations to the GABAFrontiers in molecular neuroscience · 2018Article
- γ2 GABAFrontiers in cellular neuroscience · 2018Review
- GABA transporters regulate tonic and synaptic GABAJournal of neurophysiology · 2017Article
- A versatile optical tool for studying synaptic GABAJournal of cell science · 2017Article
- Differential Alteration in Expression of Striatal GABAFrontiers in molecular neuroscience · 2017Article
- Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.The Journal of pharmacology and experimental therapeutics · 2016Article
- Pilocarpine-induced seizures trigger differential regulation of microRNA-stability related genes in rat hippocampal neurons.Scientific reports · 2016Article
- Age-Related Changes in Pre- and Postsynaptic Partners of the Cholinergic C-Boutons in Wild-Type and SOD1G93A Lumbar Motoneurons.PloS one · 2015Article
- Three epilepsy-associated GABRG2 missense mutations at the γ+/β- interface disrupt GABAA receptor assembly and trafficking by similar mechanisms but to different extents.Neurobiology of disease · 2014Article
- Long distance effect on ligand-gated ion channels extracellular domain may affect interactions with the intracellular machinery.Communicative & integrative biology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA-gated chloride channels (GABAARs) trafficking is involved in the regulation of fast inhibitory transmission. Here, we took advantage of a γ2(R43Q) subunit mutation linked to epilepsy in humans that considerably reduces the number of GABAARs on the cell surface to better understand the trafficking of GABAARs. Using recombinant expression in cultured rat hippocampal neurons and COS-7 cells, we showed that receptors containing γ2(R43Q) were addressed to the cell membrane but underwent clathrin-mediated dynamin-dependent endocytosis. The γ2(R43Q)-dependent endocytosis was reduced by GABAAR antagonists. These data, in addition to a new homology model, suggested that a conformational change in the extracellular domain of γ2(R43Q)-containing GABAARs increased their internalization. This led us to show that endogenous and recombinant wild-type GABAAR endocytosis in both cultured neurons and COS-7 cells can be amplified by their agonists. These findings revealed not only a direct relationship between endocytosis of GABAARs and a genetic neurological disorder but also that trafficking of these receptors can be modulated by their agonist.
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