ArticleNature communications2022
Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 20 citations in OpenAlex.
- Cryo-EM structures of higher order Gephyrin oligomers reveal principles of inhibitory postsynaptic scaffold organization.Nature communications · 2026Article
- Identification of CaVβ1 Isoforms Required for Neuromuscular Junction Formation and Maintenance.Cells · 2025Article
- Comprehensive characterization of the RNA editing landscape in the human aging brains with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity.Current opinion in neurobiology · 2025Review
- Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner.Communications biology · 2024Article
- Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABACommunications biology · 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
- Revisiting the development of cerebellar inhibitory interneurons in the light of single-cell genetic analyses.Histochemistry and cell biology · 2024Review
- miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.bioRxiv : the preprint server for biology · 2023Article
- Automated Image Analysis Reveals Different Localization of Synaptic Gephyrin C4 Splice Variants.eNeuro · 2023Article
- Molybdenum Cofactor Deficiency in Humans.Molecules (Basel, Switzerland) · 2022Review
- Intragenic L1 Insertion: One Possibility of Brain Disorder.Life (Basel, Switzerland) · 2022Review
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Authors and funding
13 authors at 5 institutions in 2 countries.
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Abstract
Gephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and gamma-aminobutyric acid A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defects reported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.
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