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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...

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Autores principales: Rangrez, Ashraf Yusuf, Bernt, Alexander, Poyanmehr, Reza, Harazin, Violetta, Boomgaarden, Inka, Kuhn, Christian, Rohrbeck, Astrid, Frank, Derk, Frey, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
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.
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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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