Mitsugumin 29 regulates t-tubule architecture in the failing heart

Abstract Transverse tubules (t-tubules) are uniquely-adapted membrane invaginations in cardiac myocytes that facilitate the synchronous release of Ca2+ from internal stores and subsequent myofilament contraction, although these structures become disorganized and rarefied in heart failure. We previou...

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Autores principales:	Robert N. Correll, Jeffrey M. Lynch, Tobias G. Schips, Vikram Prasad, Allen J. York, Michelle A. Sargent, Didier X. P. Brochet, Jianjie Ma, Jeffery D. Molkentin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e0793bad17014a878298a6f75b5f43f6
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spelling	oai:doaj.org-article:e0793bad17014a878298a6f75b5f43f62021-12-02T16:06:50ZMitsugumin 29 regulates t-tubule architecture in the failing heart10.1038/s41598-017-05284-22045-2322https://doaj.org/article/e0793bad17014a878298a6f75b5f43f62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05284-2https://doaj.org/toc/2045-2322Abstract Transverse tubules (t-tubules) are uniquely-adapted membrane invaginations in cardiac myocytes that facilitate the synchronous release of Ca2+ from internal stores and subsequent myofilament contraction, although these structures become disorganized and rarefied in heart failure. We previously observed that mitsugumin 29 (Mg29), an important t-tubule organizing protein in skeletal muscle, was induced in the mouse heart for the first time during dilated cardiomyopathy with heart failure. Here we generated cardiac-specific transgenic mice expressing Mg29 to model this observed induction in the failing heart. Interestingly, expression of Mg29 in the hearts of Csrp3 null mice (encoding muscle LIM protein, MLP) partially restored t-tubule structure and preserved cardiac function as measured by invasive hemodynamics, without altering Ca2+ spark frequency. Conversely, gene-deleted mice lacking both Mg29 and MLP protein showed a further reduction in t-tubule organization and accelerated heart failure. Thus, induction of Mg29 in the failing heart is a compensatory response that directly counteracts the well-characterized loss of t-tubule complexity and reduced expression of anchoring proteins such as junctophilin-2 (Jph2) that normally occur in this disease. Moreover, preservation of t-tubule structure by Mg29 induction significantly increases the function of the failing heart.Robert N. CorrellJeffrey M. LynchTobias G. SchipsVikram PrasadAllen J. YorkMichelle A. SargentDidier X. P. BrochetJianjie MaJeffery D. MolkentinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert N. Correll Jeffrey M. Lynch Tobias G. Schips Vikram Prasad Allen J. York Michelle A. Sargent Didier X. P. Brochet Jianjie Ma Jeffery D. Molkentin Mitsugumin 29 regulates t-tubule architecture in the failing heart
description	Abstract Transverse tubules (t-tubules) are uniquely-adapted membrane invaginations in cardiac myocytes that facilitate the synchronous release of Ca2+ from internal stores and subsequent myofilament contraction, although these structures become disorganized and rarefied in heart failure. We previously observed that mitsugumin 29 (Mg29), an important t-tubule organizing protein in skeletal muscle, was induced in the mouse heart for the first time during dilated cardiomyopathy with heart failure. Here we generated cardiac-specific transgenic mice expressing Mg29 to model this observed induction in the failing heart. Interestingly, expression of Mg29 in the hearts of Csrp3 null mice (encoding muscle LIM protein, MLP) partially restored t-tubule structure and preserved cardiac function as measured by invasive hemodynamics, without altering Ca2+ spark frequency. Conversely, gene-deleted mice lacking both Mg29 and MLP protein showed a further reduction in t-tubule organization and accelerated heart failure. Thus, induction of Mg29 in the failing heart is a compensatory response that directly counteracts the well-characterized loss of t-tubule complexity and reduced expression of anchoring proteins such as junctophilin-2 (Jph2) that normally occur in this disease. Moreover, preservation of t-tubule structure by Mg29 induction significantly increases the function of the failing heart.
format	article
author	Robert N. Correll Jeffrey M. Lynch Tobias G. Schips Vikram Prasad Allen J. York Michelle A. Sargent Didier X. P. Brochet Jianjie Ma Jeffery D. Molkentin
author_facet	Robert N. Correll Jeffrey M. Lynch Tobias G. Schips Vikram Prasad Allen J. York Michelle A. Sargent Didier X. P. Brochet Jianjie Ma Jeffery D. Molkentin
author_sort	Robert N. Correll
title	Mitsugumin 29 regulates t-tubule architecture in the failing heart
title_short	Mitsugumin 29 regulates t-tubule architecture in the failing heart
title_full	Mitsugumin 29 regulates t-tubule architecture in the failing heart
title_fullStr	Mitsugumin 29 regulates t-tubule architecture in the failing heart
title_full_unstemmed	Mitsugumin 29 regulates t-tubule architecture in the failing heart
title_sort	mitsugumin 29 regulates t-tubule architecture in the failing heart
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e0793bad17014a878298a6f75b5f43f6
work_keys_str_mv	AT robertncorrell mitsugumin29regulatesttubulearchitectureinthefailingheart AT jeffreymlynch mitsugumin29regulatesttubulearchitectureinthefailingheart AT tobiasgschips mitsugumin29regulatesttubulearchitectureinthefailingheart AT vikramprasad mitsugumin29regulatesttubulearchitectureinthefailingheart AT allenjyork mitsugumin29regulatesttubulearchitectureinthefailingheart AT michelleasargent mitsugumin29regulatesttubulearchitectureinthefailingheart AT didierxpbrochet mitsugumin29regulatesttubulearchitectureinthefailingheart AT jianjiema mitsugumin29regulatesttubulearchitectureinthefailingheart AT jefferydmolkentin mitsugumin29regulatesttubulearchitectureinthefailingheart
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Mitsugumin 29 regulates t-tubule architecture in the failing heart

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