ArticleDevelopmental neurobiology2015
Synaptic localization of α5 GABA (A) receptors via gephyrin interaction regulates dendritic outgrowth and spine maturation.
Article in Developmental neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- The role of GABANeuroscience and biobehavioral reviews · 2026Review
- Biphasic Memory Impairment and Recovery After Sevoflurane Exposure Are Associated With Time-Dependent Hippocampal α5-GABAAR Remodeling.CNS neuroscience & therapeutics · 2026Article
- Restoration of Extrasynaptic/Synaptic GABANeuroscience bulletin · 2026Article
- Negative allosteric modulation of α5-GABAbioRxiv : the preprint server for biology · 2026Article
- Recurrent neonatal seizures increase tonic inhibition and respond to enhancers of δ-containing GABAA receptors.JCI insight · 2025Article
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- Chronic benzodiazepine treatment triggers gephyrin scaffold destabilization and GABAFrontiers in cellular neuroscience · 2025Article
- GABA system as the cause and effect in early development.Neuroscience and biobehavioral reviews · 2024Review
- Deficits in neuronal architecture but not over-inhibition are main determinants of reduced neuronal network activity in a mouse model of overexpression of Dyrk1A.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Region and layer-specific expression of GABAFrontiers in cellular neuroscience · 2024Article
- Article
- Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.Neuropharmacology · 2023Article
- GABATrends in pharmacological sciences · 2023Review
- Nano-organization of spontaneous GABAergic transmission directs its autonomous function in neuronal signaling.Cell reports · 2022Article
- Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.Cellular and molecular neurobiology · 2022Article
- Distinct regulation of tonic GABAergic inhibition by NMDA receptor subtypes.Cell reports · 2021Article
- Sustained treatment with an α5 GABA A receptor negative allosteric modulator delays excitatory circuit development while maintaining GABAergic neurotransmission.Neuropharmacology · 2021Article
- Activity- and sleep-dependent regulation of tonic inhibition by Shisa7.Cell reports · 2021Article
- High-throughput determination of protein affinities using unmodified peptide libraries in nanomolar scale.iScience · 2021Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
GABAA receptor subunit composition is a critical determinant of receptor localization and physiology, with synaptic receptors generating phasic inhibition and extrasynaptic receptors producing tonic inhibition. Extrasynaptically localized α5 GABAA receptors are largely responsible for tonic inhibition in hippocampal neurons. However, we show here that inhibitory synapses also contain a constant level of α5 GABAA receptors throughout neuronal development, as measured by its colocalization with gephyrin, the inhibitory postsynaptic scaffolding protein. Immunoprecipitation of the α5 subunit from both cultured neurons and adult rat brain coimmunoprecipitated gephyrin, confirming this interaction in vivo. Furthermore, the α5 subunit can interact with gephyrin independent of other synaptically localized alpha subunits, as shown by immunoprecipitation experiments in HEK cells. By replacing the α5 predicted gephyrin binding domain (Residues 370-385) with either the high affinity gephyrin binding domain of the α2 subunit or homologous residues from the extrasynaptic α4 subunit that does not interact with gephyrin, α5 GABAA receptor localization shifted into or out of the synapse, respectively. These shifts in the ratio of synaptic/extrasynaptic α5 localization disrupted dendritic outgrowth and spine maturation. In contrast to the predominant view of α5 GABAA receptors being extrasynaptic and modulating tonic inhibition, we identify an intimate association of the α5 subunit with gephyrin, resulting in constant synaptic levels of α5 GABAA R throughout circuit formation that regulates neuronal development.
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