ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Gephyrin oligomerization controls GlyR mobility and synaptic clustering.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 85 citations in OpenAlex.
- Redox-dependent synaptic clustering of gephyrin.Nature communications · 2026Article
- Redox-Activated Probes Enable High-Contrast Live Imaging of Native Postsynaptic Scaffolds.Angewandte Chemie (International ed. in English) · 2026Article
- Revealing acute consequences of rapid degradation of synaptic fusion proteins at individual synapses using Auxin-Inducible Degron 2 technology.Communications biology · 2025Article
- Gephyrin filaments represent the molecular basis of inhibitory postsynaptic densities.Nature communications · 2025Article
- Thermodynamic modulation of gephyrin condensation by inhibitory synapse components.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Versatile Synthetic Affinity Probe Reveals Inhibitory Synapse Ultrastructure and Brain Connectivity.Angewandte Chemie (International ed. in English) · 2022Article
- Reciprocal stabilization of glycine receptors and gephyrin scaffold proteins at inhibitory synapses.Biophysical journal · 2021Article
- Impaired formation of high-order gephyrin oligomers underlies gephyrin dysfunction-associated pathologies.iScience · 2021Article
- Article
- Inhibitory Receptor Diffusion Dynamics.Frontiers in molecular neuroscience · 2019Article
- Article
- Heterogeneous Signaling at GABA and Glycine Co-releasing Terminals.Frontiers in synaptic neuroscience · 2018Article
- Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers.Scientific reports · 2017Article
- Cooperative stochastic binding and unbinding explain synaptic size dynamics and statistics.PLoS computational biology · 2017Article
- In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals Differences between Functional Classes of Motoneurons in Zebrafish.Current biology : CB · 2017Article
- An aggregation-removal model for the formation and size determination of post-synaptic scaffold domains.PLoS computational biology · 2017Article
- Glycinergic dysfunction in a subpopulation of dorsal horn interneurons in a rat model of neuropathic pain.Scientific reports · 2016Article
- Structure and Pharmacologic Modulation of Inhibitory Glycine Receptors.Molecular pharmacology · 2016Review
- Small fluorescence-activating and absorption-shifting tag for tunable protein imaging in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Repetitive magnetic stimulation induces plasticity of inhibitory synapses.Nature communications · 2016Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High local concentrations of glycine receptors (GlyRs) at inhibitory postsynaptic sites are achieved through their binding to the scaffold protein gephyrin. The N- and C-terminal domains of gephyrin are believed to trimerize and dimerize, respectively, thus contributing to the formation of submembranous gephyrin clusters at synapses. GlyRs are associated with gephyrin also at extrasynaptic locations. We have investigated how gephyrin oligomerization influences GlyR dynamics and clustering in COS-7 cells and in cultured spinal cord neurons. To this aim, we have expressed isolated N- and C-terminal domains of gephyrin that interfere with the oligomerization of the full-length protein. We also studied the effect of an endogenous splice variant, ge(2,4,5), with a decreased propensity to trimerize. A reduction of the size and number of gephyrin-GlyR clusters was found in cells expressing the various interfering gephyrin constructs. Using fluorescence recovery after photobleaching, we studied the exchange kinetics of synaptic gephyrin clusters. Real-time single-particle tracking was used to analyze the mobility of GlyRs. We found that all the tested constructs displayed faster rates of recovery than wild-type gephyrin and increased the mobility of extrasynaptic receptors, showing that gephyrin-gephyrin interactions modulate the lateral diffusion of GlyRs. Furthermore, we observed an inverse correlation between GlyR diffusion properties and gephyrin cluster size that depended on the number of binding sites blocked by the different constructs. Since alterations in the oligomerization properties of gephyrin are related to the dynamics of GlyRs, the gephyrin splice variant ge(2,4,5) may be implicated in the modulation of synaptic strength.
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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.