ArticleProceedings of the National Academy of Sciences of the United States of America2013
ErbB4 reduces synaptic GABAA currents independent of its receptor tyrosine kinase activity.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Orexins and neuregulins as exemplars of peptide physiology in the brain: experimental challenges and implications for neuropathology.Frontiers in cellular neuroscience · 2026Article
- Gonadotropin-releasing hormone alleviates chronic pain-related depression in male mice by rebalancing the anterior cingulate cortex excitatory-inhibitory processes via the protein kinase C/Erb-B2 receptor tyrosine kinase 4 pathway.Brain communications · 2026Article
- Multiple Roles for Neuregulins and Their v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog Receptors in Neurodegenerative Disease Pathogenesis and Therapy.The American journal of pathology · 2025Review
- Dynamic effects of ventral hippocampal NRG3/ERBB4 signaling on nicotine withdrawal-induced responses.Neuropharmacology · 2024Article
- NKCC1 to KCC2 mRNA Ratio in Schizophrenia and Its Psychopathology: a Case-Control Study.Journal of molecular neuroscience : MN · 2022Article
- Developmental, neurochemical, and behavioral analyses of ErbB4 Cyt-1 knockout mice.Journal of neurochemistry · 2022Article
- ErbB4 in the brain: Focus on high grade glioma.Frontiers in oncology · 2022Review
- Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets RevealsFrontiers in aging neuroscience · 2022Article
- ERBB4 exonic deletions on chromosome 2q34 in patients with intellectual disability or epilepsy.European journal of human genetics : EJHG · 2021Article
- ErbB4 promotes inhibitory synapse formation by cell adhesion, independent of its kinase activity.Translational psychiatry · 2021Article
- The ketogenic diet increases Neuregulin 1 expression via elevating histone acetylation and its anti-seizure effect requires ErbB4 kinase activity.Cell & bioscience · 2021Article
- Deletion of ErbB4 Disrupts Synaptic Transmission and Long-Term Potentiation of Thalamic Input to Amygdalar Medial Paracapsular Intercalated Cells.Frontiers in synaptic neuroscience · 2021Article
- ErbB4 signaling in dopaminergic axonal projections increases extracellular dopamine levels and regulates spatial/working memory behaviors.Molecular psychiatry · 2018Article
- Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons.The EMBO journal · 2018Article
- Neuregulin-2 ablation results in dopamine dysregulation and severe behavioral phenotypes relevant to psychiatric disorders.Molecular psychiatry · 2018Article
- Article
- Neuregulin-Dependent Regulation of Fast-Spiking Interneuron Excitability Controls the Timing of the Critical Period.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Dysregulated ErbB4 Splicing in Schizophrenia: Selective Effects on Parvalbumin Expression.The American journal of psychiatry · 2016Article
- Interneuron epigenomes during the critical period of cortical plasticity: Implications for schizophrenia.Neurobiology of learning and memory · 2015Review
- A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling.Nature communications · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
ErbB4 signaling in the central nervous system is implicated in neuropsychiatric disorders and epilepsy. In cortical tissue, ErbB4 associates with excitatory synapses located on inhibitory interneurons. However, biochemical and histological data described herein demonstrate that the vast majority of ErbB4 is extrasynaptic and detergent-soluble. To explore the function of this receptor population, we used unbiased proteomics, in combination with electrophysiological, biochemical, and cell biological techniques, to identify a clinically relevant ErbB4-interacting protein, the GABAA receptor α1 subunit (GABAR α1). We show that ErbB4 and GABAR α1 are robustly coexpressed in hippocampal interneurons, and that ErbB4-null mice have diminished cortical GABAR α1 expression. Moreover, we characterize a Neuregulin-mediated ErbB4 signaling modality, independent of receptor tyrosine kinase activity, that couples ErbB4 to decreased postsynaptic GABAR currents on inhibitory interneurons. Consistent with an evolving understanding of GABAR trafficking, this pathway requires both clathrin-mediated endocytosis and protein kinase C to reduce GABAR inhibitory currents, surface GABAR α1 expression, and colocalization with the inhibitory postsynaptic protein gephyrin. Our results reveal a function of ErbB4, independent of its tyrosine kinase activity, that modulates postsynaptic inhibitory control of hippocampal interneurons and may provide a novel pharmacological target in the treatment of neuropsychiatric disorders and epilepsy.
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Registered trials
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.