ArticleThe Journal of biological chemistry2012
GABRB3 mutation, G32R, associated with childhood absence epilepsy alters α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor expression and channel gating.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.Epilepsy & behavior : E&B · 2025Article
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.medRxiv : the preprint server for health sciences · 2025Article
- GABAJournal of neurochemistry · 2024Review
- Case Report: A developmental and epileptic encephalopathy 45 due toFrontiers in pediatrics · 2024Article
- Phenols and GABAFrontiers in pharmacology · 2024Review
- Variable Expression of GABAA Receptor Subunit Gamma 2 Mutation in a Nuclear Family Displaying Developmental and Encephalopathic Phenotype.International journal of molecular sciences · 2022Review
- Known and Unexplored Post-Translational Modification Pathways in Schizophrenia.Advances in experimental medicine and biology · 2022Article
- Intricacies of GABAInternational journal of molecular sciences · 2021Review
- Dravet syndrome-associated mutations inBrain communications · 2021Article
- Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy.Molecular brain · 2019Article
- Genetic and Molecular Regulation of Extrasynaptic GABA-A Receptors in the Brain: Therapeutic Insights for Epilepsy.The Journal of pharmacology and experimental therapeutics · 2018Review
- Article
- Rem2 signaling affects neuronal structure and function in part by regulation of gene expression.Molecular and cellular neurosciences · 2017Article
- GABAScientific reports · 2017Article
- [Research advances in hereditary epilepsy and precision drug therapy].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2017Review
- Differential Alteration in Expression of Striatal GABAFrontiers in molecular neuroscience · 2017Article
- Epileptic encephalopathy de novo GABRB mutations impair γ-aminobutyric acid type A receptor function.Annals of neurology · 2016Article
- Genetic neurological channelopathies: molecular genetics and clinical phenotypes.Journal of neurology, neurosurgery, and psychiatry · 2016Review
- Introduced Amino Terminal Epitopes Can Reduce Surface Expression of Neuronal Nicotinic Receptors.PloS one · 2016Article
- Article
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4 authors at 1 institution in 1 country.
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Abstract
A GABA(A) receptor β3 subunit mutation, G32R, has been associated with childhood absence epilepsy. We evaluated the possibility that this mutation, which is located adjacent to the most N-terminal of three β3 subunit N-glycosylation sites, might reduce GABAergic inhibition by increasing glycosylation of β3 subunits. The mutation had three major effects on GABA(A) receptors. First, coexpression of β3(G32R) subunits with α1 or α3 and γ2L subunits in HEK293T cells reduced surface expression of γ2L subunits and increased surface expression of β3 subunits, suggesting a partial shift from ternary αβ3γ2L receptors to binary αβ3 and homomeric β3 receptors. Second, β3(G32R) subunits were more likely than β3 subunits to be N-glycosylated at Asn-33, but increases in glycosylation were not responsible for changes in subunit surface expression. Rather, both phenomena could be attributed to the presence of a basic residue at position 32. Finally, α1β3(G32R)γ2L receptors had significantly reduced macroscopic current density. This reduction could not be explained fully by changes in subunit expression levels (because γ2L levels decreased only slightly) or glycosylation (because reduction persisted in the absence of glycosylation at Asn-33). Single channel recording revealed that α1β3(G32R)γ2L receptors had impaired gating with shorter mean open time. Homology modeling indicated that the mutation altered salt bridges at subunit interfaces, including regions important for subunit oligomerization. Our results suggest both a mechanism for mutation-induced hyperexcitability and a novel role for the β3 subunit N-terminal α-helix in receptor assembly and gating.
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