ArticleCell communication and signaling : CCS2014
TrkB interacts with ErbB4 and regulates NRG1-induced NR2B phosphorylation in cortical neurons before synaptogenesis.
Article in Cell communication and signaling : CCS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 22 citations in OpenAlex.
- ErbB signaling in brain injury regeneration: Pathway interactions and therapeutic potential.Neural regeneration research · 2026Article
- A triple serine motif in the intracellular domain of SorCS2 impacts its cellular signaling.iScience · 2025Article
- Disrupted neuregulin 1-ErbB4 signaling: Consequences of prenatal morphine exposure in rat pups and molecular gateway to neurological impairment.Toxicology reports · 2024Article
- Investigating the Interactive Effects of Sex Steroid Hormones and Brain-Derived Neurotrophic Factor during Adolescence on Hippocampal NMDA Receptor Expression.International journal of endocrinology · 2018Article
- Transglutaminase 2 overexpression induces depressive-like behavior and impaired TrkB signaling in mice.Molecular psychiatry · 2017Article
- Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1.Scientific reports · 2016Article
- Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus.Journal of neurodevelopmental disorders · 2016Article
- Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats.Developmental neuroscience · 2016Article
- Modulation of schizophrenia-related genes in the forebrain of adolescent and adult rats exposed to maternal immune activation.Schizophrenia research · 2015Article
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2 authors at 1 institution in 1 country.
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Abstract
backgroundNeuregulin 1 (NRG1) and NMDARs play important roles in various neuronal functions including neural development. NMDARs also promote many cellular events such as proliferation and survival of neuroblasts before synapse formation. Although many recent studies have indicated that NRG1 regulates NMDAR function in cortical neurons, the effect of NRG1 on NMDAR activation before synapse formation is not well studied.
resultsNRG1 induces activation of NMDAR subunit NR2B, and tropomyosin-related kinase receptor B (TrkB), the receptor for BDNF via activation of phospholipase C-gamma (PLC-γ) in immature primary cortical neurons. Our data using TrkB inhibitor (K252a), TrkB siRNA and TrkB-/- neurons demonstrated that TrkB inhibition suppresses NRG1-induced NR2B activation in neurons. We found that NRG1 stimulation leads to GABAA receptor-mediated TrkB activation. Co-immunoprecipitation and proximity ligase assay showed that TrkB interacts with ErbB4 (NRG1 receptor) and the TrkB-ErbB4 interaction was increased following NRG1 treatment. A significant reduction in TrkB-ErbB4 interaction was observed in the prefrontal cortex of schizophrenia subjects. We found significant increase in released BDNF levels following NRG1 treatment, which was inhibited by ErbB4 inhibitor, AG1478. In addition, pretreatment with BDNF neutralizing antibody, but not control IgG abolished NRG1-induced increases in phospho-TrkB and phospho-NR2B levels. Moreover, studies using TrkB mutants showed that intercellular domain of TrkB is necessary for TrkB-ErbB4 interaction and NR2B activation.
conclusionsBDNF/TrkB signaling plays an important role in the NRG1-stimulated NR2B regulation. These findings could be of relevance to many neurodevelopmental disorders, as NRG1 and BDNF signaling pathways have been implicated in autism and schizophrenia.
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