ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Processing of neuregulin-1 by neuropsin regulates GABAergic neuron to control neural plasticity of the mouse hippocampus.
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 41 papers.
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41 citing papers in PubMed, 67 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
- Exploration of schizophrenia-related behavioral and molecular abnormalities in a mutant mouse model with a mutation in the TVV motif of the ErbB4 gene.Molecular brain · 2025Article
- Investigation on the Substrate Specificity of Serine Protease Neuropsin by Molecular Dynamics Simulation and Marmoset Gene Atlas (MGA).ACS omega · 2025Article
- KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation in male mice.Theranostics · 2025Article
- Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1.Cell death & disease · 2023Article
- Blood Kallikrein-8 and Non-Amnestic Mild Cognitive Impairment: An Exploratory Study.Journal of Alzheimer's disease reports · 2023Article
- Investigation on substrate specificity and catalytic activity of serine protease neuropsin.Biophysics and physicobiology · 2022Article
- Is kallikrein-8 a blood biomarker for detecting amnestic mild cognitive impairment? Results of the population-based Heinz Nixdorf Recall study.Alzheimer's research & therapy · 2021Article
- Roles and Mechanisms of Axon-Guidance Molecules in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Oral Administration of ProbioticBiomedicines · 2021Article
- A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis.Theranostics · 2021Article
- Neuropsin in mental health.The journal of physiological sciences : JPS · 2020Review
- Involvement of Kallikrein-Related Peptidases in Nervous System Disorders.Frontiers in cellular neuroscience · 2020Article
- NMDA Receptors Regulate Neuregulin 2 Binding to ER-PM Junctions and Ectodomain Release by ADAM10 [corrected].Molecular neurobiology · 2019Article
- Review
- Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling.Circulation · 2019Article
- Neuregulin directed molecular mechanisms of visual cortical plasticity.The Journal of comparative neurology · 2019Review
- Article
- Higher levels of kallikrein-8 in female brain may increase the risk for Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2018Article
- Altered hippocampal gene expression and structure in transgenic mice overexpressing neuregulin 1 (Nrg1) type I.Translational psychiatry · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protease-mediated signaling is an important modulator of the nervous system. However, identifying the specific signaling substrates of such proteases is limited by the rapidity with which intermediate substrate forms are cleaved and released. Here, a screening method to detect noncleaved enzyme-bound forms was developed and used to identify a novel neuropsin/neuregulin-1 (NRG-1) proteolytic signaling system, which is specifically localized in the microdomain of synaptic cleft, in the mouse hippocampus. The extracellular protease, neuropsin, cleaved mature NRG-1 (comprising the extracellular domain of the NRG-1) at three newly identified sites to remove the heparin-binding domain of NRG-1. This released the ligand moiety from the matrix-glycosaminoglycan pool and enabled it to trigger the phosphorylation of NRG-1 receptor, p185 (ErbB4). Proteolysis of mature NRG-1 by neuropsin led to colocalization of the processed NRG-1 with ErbB4 in parvalbumin-positive hippocampal interneurons and consequent phosphorylation of tyrosine residues of proteins in the cells. Moreover, neuropsin knock-out mice exhibited impairments in Schaffer collateral early phase long-term potentiation, and application of the recombinant NRG-1 lacking heparin-binding activity reversed the effects through the activation of ErbB4 and GABA(A) receptors. Thus, ErbB4 signaling induced by neuropsin-dependent processing of NRG-1 contributes to the modulation of synaptic plasticity via regulation of GABAergic transmission. This signaling system may be involved in human cognition and mental disorders, such as schizophrenia and bipolar disorder, by its dysfunction.
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