ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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108 citing papers in PubMed, 221 citations in OpenAlex.
- Levetiracetam restores GABAergic function and network homeostasis following Vps35 deficiency in excitatory neurons.Translational neurodegeneration · 2026Article
- Synaptic vs. Non-Synaptic Glycine Receptors: Physiological Role and Implications in Alzheimer's Disease Pathology.International journal of molecular sciences · 2026Review
- GABACellular and molecular neurobiology · 2026Review
- Binding patterns of glycine receptor autoantibodies are related to clinical syndromes.Acta neuropathologica communications · 2025Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Glycine receptor activation promotes pancreatic islet cell proliferation via the PI3K/mTORC1/p70S6K pathway.JCI insight · 2025Article
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- γ1 GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A zebrafish gephyrinb mutant distinguishes synaptic and enzymatic functions of Gephyrin.Neural development · 2024Article
- Gephyrin promotes autonomous assembly and synaptic localization of GABAergic postsynaptic components without presynaptic GABA release.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Case report: A case of anti-glycine receptor encephalomyelitis triggered by post-transplant or COVID-19 infection?Frontiers in neurology · 2024Article
- Neuroplastin exerts antiepileptic effects through binding to the α1 subunit of GABA type A receptors to inhibit the internalization of the receptors.Journal of translational medicine · 2023Article
- Blue Native PAGE-Antibody Shift in Conjunction with Mass Spectrometry to Reveal Protein Subcomplexes: Detection of a Cerebellar α1/α6-Subunits Containing γ-Aminobutyric Acid Type A Receptor Subtype.International journal of molecular sciences · 2023Article
- Inhibitory Synaptic Influences on Developmental Motor Disorders.International journal of molecular sciences · 2023Review
- Nano-organization of spontaneous GABAergic transmission directs its autonomous function in neuronal signaling.Cell reports · 2022Article
- Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.Cellular and molecular neurobiology · 2022Article
- Gephyrin Interacts with the K-Cl Cotransporter KCC2 to Regulate Its Surface Expression and Function in Cortical Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Regulation of Inhibitory Signaling at the Receptor and Cellular Level; Advances in Our Understanding of GABAergic Neurotransmission and the Mechanisms by Which It Is Disrupted in Epilepsy.Frontiers in synaptic neuroscience · 2022Review
- Stepwise disassembly of GABAergic synapses during pathogenic excitotoxicity.Cell reports · 2021Article
- Gephyrin-Lacking PV Synapses on Neocortical Pyramidal Neurons.International journal of molecular sciences · 2021Article
48 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
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Abstract
The role of the scaffolding protein gephyrin at hippocampal inhibitory synapses is not well understood. A previous study (Kneussel et al., 1999) reported a complete loss of synaptic clusters of the major GABA(A)R subunits alpha2 and gamma2 in hippocampal neurons lacking gephyrin. In contrast, we show here that GABA(A)R alpha2 and gamma2 subunits do cluster at pyramidal synapses in hippocampal cultures from gephyrin-/- mice, albeit at reduced levels compared with control neurons. Synaptic aggregation of GABA(A)R alpha1 on interneurons was identical between the culture types. Furthermore, we recorded miniature IPSCs (mIPSCs) from gephyrin-/- neurons. Although the mean mIPSC amplitude was reduced (by 23%) compared with control, the frequency of these events was unchanged. Cell surface labeling experiments indicated that gephyrin contributes, in part, to aggregation but not to insertion or stabilization of GABA(A)R alpha2 and gamma2 in the plasma membrane. Thus, a major gephyrin-independent component of hippocampal inhibitory synapse development must exist. We also report that glycine receptors cluster at GABAergic synapses in a subset of hippocampal interneurons and pyramidal neurons. Unlike GABA(A)Rs, synaptic clustering of glycine receptors was completely abolished in gephyrin-/- neurons. Finally, artificial extrasynaptic aggregation of GABA(A)R was able to redistribute and cocluster gephyrin by a mechanism requiring a neuron-specific modification or intermediary protein. We propose a model of hippocampal inhibitory synapse development in which some GABA(A)Rs cluster at synapses by a gephyrin-independent mechanism and recruit gephyrin. This clustered gephyrin may then recruit glycine receptors, additional GABA(A)Rs, and other signal-transducing components.
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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.