ArticleThe Journal of biological chemistry2009
Transcriptional interaction of an estrogen receptor splice variant and ErbB4 suggests convergence in gene susceptibility pathways in schizophrenia.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia.Molecular psychiatry · 2015Trial
- Systems-Level Analysis of Genetic Variants Reveals Functional and Spatiotemporal Context in Treatment-resistant Schizophrenia.Molecular neurobiology · 2022Article
- Sex Differences in Verbal Memory Predict Functioning Through Negative Symptoms in Early Psychosis.Schizophrenia bulletin · 2020Article
- Estrogen Receptor β Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.Molecular neurobiology · 2018Article
- Nuclear Receptors and Neuroinflammation in Schizophrenia.Molecular neuropsychiatry · 2018Article
- Cooperation of Genomic and Rapid Nongenomic Actions of Estrogens in Synaptic Plasticity.Molecular neurobiology · 2017Review
- Article
- HNRNP G and HTRA2-BETA1 regulate estrogen receptor alpha expression with potential impact on endometrial cancer.BMC cancer · 2015Article
- Convergent and divergent cellular responses by ErbB4 isoforms in mammary epithelial cells.Molecular cancer research : MCR · 2014Article
- Distinct phenotypes of new transmembrane-domain neuregulin 1 mutant mice and the rescue effects of valproate on the observed schizophrenia-related cognitive deficits.Frontiers in behavioral neuroscience · 2014Article
- Receptor tyrosine kinases in the nucleus.Cold Spring Harbor perspectives in biology · 2013Review
- Cell Models for the Study of Sex Steroid Hormone Neurobiology.Journal of steroids & hormonal science · 2012Article
- Estrogen-induced upregulation of Sftpb requires transcriptional control of neuregulin receptor ErbB4 in mouse lung type II epithelial cells.Biochimica et biophysica acta · 2011Article
- Genomics and pharmacogenomics of schizophrenia.CNS neuroscience & therapeutics · 2011Review
- Rapid estradiol modulation of neuronal connectivity and its implications for disease.Frontiers in endocrinology · 2011Article
- Sex-dependent antipsychotic capacity of 17β-estradiol in the latent inhibition model: a typical antipsychotic drug in both sexes, atypical antipsychotic drug in males.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2010Article
- Article
- Selection of reference gene expression in a schizophrenia brain cohort.The Australian and New Zealand journal of psychiatry · 2010Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mounting evidence from clinical and basic research suggests that estrogen signaling may be altered in the brains of people with schizophrenia. Previously, we found that DNA sequence variation in the estrogen receptor (ER) alpha gene, lower ERalpha mRNA levels, and/or blunted ERalpha signaling is associated with schizophrenia. In this study, we asked whether the naturally occurring truncated ERalpha isoform, Delta7, which acts as a dominant negative, can attenuate gene expression induced by the wild-type (WT) receptor in an estrogen-dependent manner in neuronal (SHSY5Y) and non-neuronal (CHOK1 and HeLa) cells. In addition, we determined the extent to which ERalpha interacts with NRG1-ErbB4, a leading schizophrenia susceptibility pathway. Reductions in the transcriptionally active form of ErbB4 comprising the intracytoplasmic domain (ErbB4-ICD) have been found in schizophrenia, and we hypothesized that ERalpha and ErbB4 may converge to control gene expression. In the present study, we show that truncated Delta7-ERalpha attenuates WT-ERalpha-driven gene expression across a wide range of estrogen concentrations in cells that express functional ERalpha at base line or upon co-transfection of full-length ERalpha. Furthermore, we find that ErbB4-ICD can potentiate the transcriptional activity of WT-ERalpha at EREs in two cell lines and that this potentiation effect is abolished by the presence of Delta7-ERalpha. Immunofluorescence microscopy revealed nuclear co-localization of WT-ERalpha, Delta7-ERalpha, and ErbB4-ICD, whereas immunoprecipitation assays showed direct interaction. Our findings demonstrate convergence between ERalpha and ErbB4-ICD in the transcriptional control of ERalpha-target gene expression and suggest that this may represent a convergent pathway that may be disrupted in schizophrenia.
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