ArticleThe Journal of biological chemistry2012
Splice-specific glycine receptor binding, folding, and phosphorylation of the scaffolding protein gephyrin.
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 46 papers.
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Who cites it
46 citing papers in PubMed.
- Impaired gephyrin G-domain trimerization and phase separation in a patient with developmental epileptic encephalopathy.EMBO molecular medicine · 2026Article
- Cryo-EM structures of higher order Gephyrin oligomers reveal principles of inhibitory postsynaptic scaffold organization.Nature communications · 2026Article
- Autism-associated ARHGEF9 variants impair GABAergic synapses and ultrasonic communication by reducing gephyrin phosphorylation.Molecular psychiatry · 2026Article
- Molecular Physiology of the Neuronal Synapse.Current issues in molecular biology · 2026Review
- Gephyrin filaments represent the molecular basis of inhibitory postsynaptic densities.Nature communications · 2025Article
- Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin.Journal of neurochemistry · 2025Article
- Wheel-Running Exercise Alleviates Anxiety-Like Behavior via Down-Regulating S-Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A zebrafish gephyrinb mutant distinguishes synaptic and enzymatic functions of Gephyrin.Neural development · 2024Article
- Thermodynamic modulation of gephyrin condensation by inhibitory synapse components.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The History of Animal and Plant Sulfite Oxidase-A Personal View.Molecules (Basel, Switzerland) · 2023Review
- Eukaryotic-like gephyrin and cognate membrane receptor coordinate corynebacterial cell division and polar elongation.Nature microbiology · 2023Article
- Eukaryotic-like gephyrin and cognate membrane receptor coordinate corynebacterial cell division and polar elongation.bioRxiv : the preprint server for biology · 2023Article
- Automated Image Analysis Reveals Different Localization of Synaptic Gephyrin C4 Splice Variants.eNeuro · 2023Article
- Binding of gephyrin to microtubules is regulated by its phosphorylation at Ser270.Histochemistry and cell biology · 2021Article
- Gephyrin-mediated formation of inhibitory postsynaptic density sheet via phase separation.Cell research · 2021Article
- High-throughput determination of protein affinities using unmodified peptide libraries in nanomolar scale.iScience · 2021Article
- Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions.Neuroscience · 2020Review
- A Sam68-dependent alternative splicing program shapes postsynaptic protein complexes.The European journal of neuroscience · 2019Article
- Nanoscale Subsynaptic Domains Underlie the Organization of the Inhibitory Synapse.Cell reports · 2019Article
- Gephyrin: a key regulatory protein of inhibitory synapses and beyond.Histochemistry and cell biology · 2018Review
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2 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The multimeric scaffolding protein gephyrin forms post-synaptic clusters at inhibitory sites, thereby anchoring inhibitory glycine (GlyR) and subsets of γ-aminobutyric acid type A (GABAA) receptors. Gephyrin is composed of three domains, the conserved N-terminal G- and C-terminal E-domain, connected by the central (C-) domain. In this study we investigated the oligomerization, folding and stability, GlyR β-loop binding, and phosphorylation of three gephyrin splice variants (Geph, Geph-C3, Geph-C4) after expression and purification from insect cells (Sf9). In contrast to Escherichia coli-derived trimeric gephyrin, we found that Sf9 gephyrins form hexamers as basic oligomeric form. In the case of Geph and Geph-C4, also high-oligomeric forms (∼900 kDa) were isolated. Partial proteolysis revealed a compact folding of the Gephyrin G and C domain in one complex, whereas a much lower stability for the E domain was found. After GlyR β-loop binding, the stability of the E domain increased in Geph and Geph-C4 significantly. In contrast, the E domain in Geph-C3 is less stable and binds the GlyR β-loop with one order of magnitude lower affinity. Finally, we identified 18 novel phosphorylation sites in gephyrin, of which all except one are located within the C domain. We propose two models for the domain arrangement in hexameric gephyrin based on the oligomerization of either the E or C domains, with the latter being crucial for the regulation of gephyrin clustering.
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