ArticleProceedings of the National Academy of Sciences of the United States of America2013
Collybistin activation by GTP-TC10 enhances postsynaptic gephyrin clustering and hippocampal GABAergic neurotransmission.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 45 citations in OpenAlex.
- Hearing loss associated with CDC42 in mice and humans (Takenouchi-Kosaki syndrome): CDC42 and RHOQ synergistically function in cochlear hair cells.The Journal of biological chemistry · 2026Article
- Phosphoinositide- and Collybistin-Dependent Synaptic Clustering of Gephyrin.Journal of neurochemistry · 2025Article
- Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner.Communications biology · 2024Article
- Loss of CDKL5 Causes Synaptic GABAergic Defects That Can Be Restored with the Neuroactive Steroid Pregnenolone-Methyl-Ether.International journal of molecular sciences · 2022Article
- Differential modulation of collybistin conformational dynamics by the closely related GTPases Cdc42 and TC10.Frontiers in synaptic neuroscience · 2022Article
- Neuroligin-2 dependent conformational activation of collybistin reconstituted in supported hybrid membranes.The Journal of biological chemistry · 2020Article
- Identification of Key Genes and the Pathophysiology Associated With Major Depressive Disorder Patients Based on Integrated Bioinformatics Analysis.Frontiers in psychiatry · 2020Article
- Targeting GABAFrontiers in molecular neuroscience · 2019Article
- Mutation p.R356Q in the Collybistin Phosphoinositide Binding Site Is Associated With Mild Intellectual Disability.Frontiers in molecular neuroscience · 2019Article
- Inhibition of the mevalonate pathway enhances cancer cell oncolysis mediated by M1 virus.Nature communications · 2018Article
- Synaptic Plasticity and Excitation-Inhibition Balance in the Dentate Gyrus: Insights fromNeural plasticity · 2018Review
- Article
- Generation of pure GABAergic neurons by transcription factor programming.Nature methods · 2017Article
- In vivo transgenic expression of collybistin in neurons of the rat cerebral cortex.The Journal of comparative neurology · 2017Article
- Regulation of GABAergic synapse development by postsynaptic membrane proteins.Brain research bulletin · 2017Review
- Endosomal Phosphatidylinositol 3-Phosphate Promotes Gephyrin Clustering and GABAergic Neurotransmission at Inhibitory Postsynapses.The Journal of biological chemistry · 2017Article
- Specificity of Collybistin-Phosphoinositide Interactions: IMPACT OF THE INDIVIDUAL PROTEIN DOMAINS.The Journal of biological chemistry · 2016Article
- Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.Molecular and cellular biology · 2015Article
- Lipid binding defects and perturbed synaptogenic activity of a Collybistin R290H mutant that causes epilepsy and intellectual disability.The Journal of biological chemistry · 2015Article
- Activity-dependent inhibitory synapse remodeling through gephyrin phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In many brain regions, gephyrin and GABAA receptor clustering at developing inhibitory synapses depends on the guanine nucleotide exchange factor collybistin (Cb). The vast majority of Cb splice variants contain an autoinhibitory src homology 3 domain, and several synaptic proteins are known to bind to this SH3 domain and to thereby activate gephyrin clustering. However, many functional GABAergic synapses form independently of the known Cb-activating proteins, indicating that additional Cb activators must exist. Here we show that the small Rho-like GTPase TC10 stimulates Cb-dependent gephyrin clustering by binding in its active, GTP-bound state to the pleckstrin homology domain of Cb. Overexpression of a constitutively active TC10 variant in neurons causes an increase in the density of synaptic gephyrin clusters and mean miniature inhibitory postsynaptic current amplitudes, whereas a dominant negative TC10 variant has opposite effects. The enhancement of Cb-induced gephyrin clustering by GTP-TC10 does not depend on the guanine nucleotide exchange activity of Cb but involves an interaction that resembles reported interactions of other small GTPases with their effectors. Our data indicate that GTP-TC10 activates the major src homology 3 domain-containing Cb variants by relieving autoinhibition and thus define an alternative GTPase-driven signaling pathway in the genesis of inhibitory synapses.
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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.