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Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy
Dysbindin is an established schizophrenia susceptibility gene thoroughly studied in the context of the brain. We have previously shown through a yeast two-hybrid screen that it is also a cardiac binding partner of the intercalated disc protein Myozap. Because Dysbindin is highly expressed in the hea...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840930/ https://www.ncbi.nlm.nih.gov/pubmed/24385487 http://dx.doi.org/10.1083/jcb.201303052 |
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author | Rangrez, Ashraf Yusuf Bernt, Alexander Poyanmehr, Reza Harazin, Violetta Boomgaarden, Inka Kuhn, Christian Rohrbeck, Astrid Frank, Derk Frey, Norbert |
author_facet | Rangrez, Ashraf Yusuf Bernt, Alexander Poyanmehr, Reza Harazin, Violetta Boomgaarden, Inka Kuhn, Christian Rohrbeck, Astrid Frank, Derk Frey, Norbert |
author_sort | Rangrez, Ashraf Yusuf |
collection | PubMed |
description | Dysbindin is an established schizophrenia susceptibility gene thoroughly studied in the context of the brain. We have previously shown through a yeast two-hybrid screen that it is also a cardiac binding partner of the intercalated disc protein Myozap. Because Dysbindin is highly expressed in the heart, we aimed here at deciphering its cardiac function. Using a serum response factor (SRF) response element reporter-driven luciferase assay, we identified a robust activation of SRF signaling by Dysbindin overexpression that was associated with significant up-regulation of SRF gene targets, such as Acta1 and Actc1. Concurrently, we identified RhoA as a novel binding partner of Dysbindin. Further phenotypic and mechanistic characterization revealed that Dysbindin induced cardiac hypertrophy via RhoA–SRF and MEK1–ERK1 signaling pathways. In conclusion, we show a novel cardiac role of Dysbindin in the activation of RhoA–SRF and MEK1–ERK1 signaling pathways and in the induction of cardiac hypertrophy. Future in vivo studies should examine the significance of Dysbindin in cardiomyopathy. |
format | Online Article Text |
id | pubmed-3840930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38409302014-05-25 Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy Rangrez, Ashraf Yusuf Bernt, Alexander Poyanmehr, Reza Harazin, Violetta Boomgaarden, Inka Kuhn, Christian Rohrbeck, Astrid Frank, Derk Frey, Norbert J Cell Biol Research Articles Dysbindin is an established schizophrenia susceptibility gene thoroughly studied in the context of the brain. We have previously shown through a yeast two-hybrid screen that it is also a cardiac binding partner of the intercalated disc protein Myozap. Because Dysbindin is highly expressed in the heart, we aimed here at deciphering its cardiac function. Using a serum response factor (SRF) response element reporter-driven luciferase assay, we identified a robust activation of SRF signaling by Dysbindin overexpression that was associated with significant up-regulation of SRF gene targets, such as Acta1 and Actc1. Concurrently, we identified RhoA as a novel binding partner of Dysbindin. Further phenotypic and mechanistic characterization revealed that Dysbindin induced cardiac hypertrophy via RhoA–SRF and MEK1–ERK1 signaling pathways. In conclusion, we show a novel cardiac role of Dysbindin in the activation of RhoA–SRF and MEK1–ERK1 signaling pathways and in the induction of cardiac hypertrophy. Future in vivo studies should examine the significance of Dysbindin in cardiomyopathy. The Rockefeller University Press 2013-11-25 /pmc/articles/PMC3840930/ /pubmed/24385487 http://dx.doi.org/10.1083/jcb.201303052 Text en © 2013 Rangrez et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Rangrez, Ashraf Yusuf Bernt, Alexander Poyanmehr, Reza Harazin, Violetta Boomgaarden, Inka Kuhn, Christian Rohrbeck, Astrid Frank, Derk Frey, Norbert Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy |
title | Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy |
title_full | Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy |
title_fullStr | Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy |
title_full_unstemmed | Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy |
title_short | Dysbindin is a potent inducer of RhoA–SRF-mediated cardiomyocyte hypertrophy |
title_sort | dysbindin is a potent inducer of rhoa–srf-mediated cardiomyocyte hypertrophy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840930/ https://www.ncbi.nlm.nih.gov/pubmed/24385487 http://dx.doi.org/10.1083/jcb.201303052 |
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