ArticleCell reports2022
The epilepsy-associated protein PCDH19 undergoes NMDA receptor-dependent proteolytic cleavage and regulates the expression of immediate-early genes.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- The intracellular domain of the epilepsy protein PCDH19 regulates spine density in cortical neurons in vivo viaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Diagnosis and follow-up of a PCDH19 epilepsy patient.Psychiatric genetics · 2026Article
- Neuronal activity drives PCDH9 cleavage and nuclear translocation to coordinate structural and functional remodeling.Frontiers in cellular neuroscience · 2025Article
- Development of a Proteomic Workflow for the Identification of Heparan Sulphate Proteoglycan-Binding Substrates of ADAM17.Proteomics · 2024Article
- Protective effects of pioglitazone in renal ischemia-reperfusion injury (RIRI): focus on oxidative stress and inflammation.Clinical and experimental nephrology · 2024Review
- Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway.Molecular brain · 2024Article
- Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/β-catenin signalling pathway.Molecular psychiatry · 2024Article
- Effect of PCDH19 missense mutations on cell-to-cell proximity and neuronal development under heterotypic conditions.PNAS nexus · 2024Article
- Multiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsy.Translational psychiatry · 2024Review
- Directed differentiation of human iPSCs into mesenchymal lineages by optogenetic control of TGF-β signaling.Cell reports · 2023Article
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- Modifying PCDH19 levels affects cortical interneuron migration.Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protocadherin-19 (PCDH19) is a synaptic cell-adhesion molecule encoded by X-linked PCDH19, a gene linked with epilepsy. Here, we report a synapse-to-nucleus signaling pathway through which PCDH19 bridges neuronal activity with gene expression. In particular, we describe the NMDA receptor (NMDAR)-dependent proteolytic cleavage of PCDH19, which leads to the generation of a PCDH19 C-terminal fragment (CTF) able to enter the nucleus. We demonstrate that PCDH19 CTF associates with chromatin and with the chromatin remodeler lysine-specific demethylase 1 (LSD1) and regulates expression of immediate-early genes (IEGs). Our results are consistent with a model whereby PCDH19 favors maintenance of neuronal homeostasis via negative feedback regulation of IEG expression and provide a key to interpreting PCDH19-related hyperexcitability.
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