ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
A comprehensive small interfering RNA screen identifies signaling pathways required for gephyrin clustering.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Semaglutide Alleviates LPS-Induced Cognitive Disorder via O-GlcNAcylation of AKT-mTOR Signaling Pathway Components.Neuromolecular medicine · 2026Article
- Effects of TrkB-related induced metaplasticity within the BLA on anxiety, extinction learning, and plasticity in BLA-modulated brain regions.Behavioral and brain functions : BBF · 2025Article
- Intra-BLA alteration of interneurons' modulation of activity in rats, reveals a dissociation between effects on anxiety symptoms and extinction learning.Neurobiology of stress · 2024Article
- Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus.Molecular psychiatry · 2024Article
- Dissection of signaling pathways regulating TrkB-dependent gephyrin clustering.Frontiers in molecular neuroscience · 2024Article
- Article
- Transactivation of TrkB Receptors by Oxytocin and Its G Protein-Coupled Receptor.Frontiers in molecular neuroscience · 2022Article
- Autism Spectrum Disorder Risk Factor Met Regulates the Organization of Inhibitory Synapses.Frontiers in molecular neuroscience · 2021Article
- Interference With Complex IV as a Model of Age-Related Decline in Synaptic Connectivity.Frontiers in molecular neuroscience · 2020Article
- Phosphorylation of Gephyrin in Zebrafish Mauthner Cells Governs Glycine Receptor Clustering and Behavioral Desensitization to Sound.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Glycine Protects Muscle Cells From WastingFrontiers in nutrition · 2019Article
- Gephyrin: a key regulatory protein of inhibitory synapses and beyond.Histochemistry and cell biology · 2018Review
- Loss of TrkB Signaling in Parvalbumin-Expressing Basket Cells Results in Network Activity Disruption and Abnormal Behavior.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- GABA type a receptor trafficking and the architecture of synaptic inhibition.Developmental neurobiology · 2018Review
- Endosomal Phosphatidylinositol 3-Phosphate Promotes Gephyrin Clustering and GABAergic Neurotransmission at Inhibitory Postsynapses.The Journal of biological chemistry · 2017Article
- Receptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells.Scientific reports · 2016Article
- Brain oscillations in bipolar disorder and lithium-induced changes.Neuropsychiatric disease and treatment · 2016Review
- Collybistin binds and inhibits mTORC1 signaling: a potential novel mechanism contributing to intellectual disability and autism.European journal of human genetics : EJHG · 2016Article
- Human gephyrin is encompassed within giant functional noncoding yin-yang sequences.Nature communications · 2015Article
- Combination of methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system.Experimental neurology · 2015Article
Corrections and comments
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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
The postsynaptic scaffold protein gephyrin is clustered at inhibitory synapses and serves for the stabilization of GABA(A) receptors. Here, a comprehensive kinome-wide siRNA screen in a human HeLa cell-based model for gephyrin clustering was used to identify candidate protein kinases implicated in the stabilization of gephyrin clusters. As a result, 12 hits were identified including FGFR1 (FGF receptor 1), TrkB, and TrkC as well as components of the MAPK and mammalian target of rapamycin (mTOR) pathways. For confirmation, the impact of these hits on gephyrin clustering was analyzed in rat primary hippocampal neurons. We found that brain-derived neurotrophic factor (BDNF) acts on gephyrin clustering through MAPK signaling, and this process may be controlled by the MAPK signaling antagonist sprouty2. BDNF signaling through phosphatidylinositol 3-kinase (PI3K)-Akt also activates mTOR and represses GSK3β, which was previously shown to reduce gephyrin clustering. Gephyrin is associated with inactive mTOR and becomes released upon BDNF-dependent mTOR activation. In primary neurons, a reduction in the number of gephyrin clusters due to manipulation of the BDNF-mTOR signaling is associated with reduced GABA(A) receptor clustering, suggesting functional impairment of GABA signaling. Accordingly, application of the mTOR antagonist rapamycin leads to disinhibition of neuronal networks as measured on microelectrode arrays. In conclusion, we provide evidence that BDNF regulates gephyrin clustering via MAPK as well as PI3K-Akt-mTOR signaling.
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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.