ArticleThe Journal of biological chemistry2010
Complex role of collybistin and gephyrin in GABAA receptor clustering.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 135 citations in OpenAlex.
- Article
- Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin.Journal of neurochemistry · 2025Article
- Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes.Journal of neurochemistry · 2025Review
- Impaired axon initial segment structure and function in a model ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Modular Structure and Polymerization Status of GABAInternational journal of molecular sciences · 2024Article
- Cellular and Molecular Mechanisms Regulating Retinal Synapse Development.Annual review of vision science · 2024Review
- 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
- UNC-43/CaMKII-triggered anterograde signals recruit GABANature communications · 2023Article
- Deciphering the conformational dynamics of gephyrin-mediated collybistin activation.Biophysical reports · 2022Article
- Recruitment of Plasma Membrane GABA-A Receptors by Submembranous Gephyrin/Collybistin Clusters.Cellular and molecular neurobiology · 2022Article
- GABA receptor associated protein changes the electrostatic environment around the GABA type A receptor.Proteins · 2022Article
- Differential modulation of collybistin conformational dynamics by the closely related GTPases Cdc42 and TC10.Frontiers in synaptic neuroscience · 2022Article
- A novelThe Journal of international medical research · 2021Article
- Binding of gephyrin to microtubules is regulated by its phosphorylation at Ser270.Histochemistry and cell biology · 2021Article
- A proline-rich motif in the large intracellular loop of the glycine receptor α1 subunit interacts with the Pleckstrin homology domain of collybistin.Journal of advanced research · 2021Article
- Phosphorylation on Ser-359 of the α2 subunit in GABA type A receptors down-regulates their density at inhibitory synapses.The Journal of biological chemistry · 2020Article
- Effects of GABAFrontiers in molecular neuroscience · 2020Article
- Identification of a Core Amino Acid Motif within the α Subunit of GABACell reports · 2019Article
- Preserving the balance: diverse forms of long-term GABAergic synaptic plasticity.Nature reviews. Neuroscience · 2019Review
- Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.Behavioural brain research · 2019Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Gephyrin and collybistin are key components of GABA(A) receptor (GABA(A)R) clustering. Nonetheless, resolving the molecular interactions between the plethora of GABA(A)R subunits and these clustering proteins is a significant challenge. We report a direct interaction of GABA(A)R α2 and α3 subunit intracellular M3-M4 domain (but not α1, α4, α5, α6, β1-3, or γ1-3) with gephyrin. Curiously, GABA(A)R α2, but not α3, binds to both gephyrin and collybistin using overlapping sites. The reciprocal binding sites on gephyrin for collybistin and GABA(A)R α2 also overlap at the start of the gephyrin E domain. This suggests that although GABA(A)R α3 interacts with gephyrin, GABA(A)R α2, collybistin, and gephyrin form a trimeric complex. In support of this proposal, tri-hybrid interactions between GABA(A)R α2 and collybistin or GABA(A)R α2 and gephyrin are strengthened in the presence of gephyrin or collybistin, respectively. Collybistin and gephyrin also compete for binding to GABA(A)R α2 in co-immunoprecipitation experiments and co-localize in transfected cells in both intracellular and submembrane aggregates. Interestingly, GABA(A)R α2 is capable of "activating " collybistin isoforms harboring the regulatory SH3 domain, enabling targeting of gephyrin to the submembrane aggregates. The GABA(A)R α2-collybistin interaction was disrupted by a pathogenic mutation in the collybistin SH3 domain (p.G55A) that causes X-linked intellectual disability and seizures by disrupting GABA(A)R and gephyrin clustering. Because immunohistochemistry in retina revealed a preferential co-localization of collybistin with α2 subunit containing GABA(A)Rs, but not GlyRs or other GABA(A)R subtypes, we propose that the collybistin-gephyrin complex has an intimate role in the clustering of GABA(A)Rs containing the α2 subunit.
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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.