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J. Cardiovasc. Dev. Dis. 2016, 3(2), 19; doi:10.3390/jcdd3020019

Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function

1
Division of Cardiology, Department of Medicine, Johns Hopkins University, Ross 1050, 720 Rutland Avenue, Baltimore, MD 21205, USA
2
Institute of Biotechnology & Department of Life Science, National Tsing Hua University, Hsinchu City 30013, Taiwan
3
Department of Physiology, Johns Hopkins University, Ross 1050, 720 Rutland Avenue, Baltimore, MD 21205, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Rolf Bodmer and Georg Vogler
Received: 16 February 2016 / Revised: 6 May 2016 / Accepted: 11 May 2016 / Published: 24 May 2016
(This article belongs to the Special Issue Non-mammalian Animal Models to Study Heart Development and Disease)
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Abstract

Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP’s role(s) in the heart. Its functional diversity is determined by differential binding of distinct cofactors/adapters, which is likely disrupted during disease. VCP mutations cause multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that involves inclusion body myopathy. MSP patients display progressive muscle weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory failure, which are consistent with critical myocardial roles for the enzyme. Nonetheless, efficient models to interrogate VCP in cardiac muscle remain underdeveloped and poorly studied. Here, we investigated the significance of VCP and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar organization and heart function in adult flies. Furthermore, expression of MSP disease-causing alleles engendered cardiomyopathy in adults and structural defects in embryonic hearts. Drosophila may therefore serve as a valuable model for examining role(s) of VCP in cardiogenesis and for identifying novel heart-specific VCP interactions, which when disrupted via mutation, contribute to or elicit cardiac pathology. View Full-Text
Keywords: TER94; cdc48; p97; myopathy; multisystem proteinopathy; IBMPFD TER94; cdc48; p97; myopathy; multisystem proteinopathy; IBMPFD
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MDPI and ACS Style

Viswanathan, M.C.; Blice-Baum, A.C.; Sang, T.-K.; Cammarato, A. Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function. J. Cardiovasc. Dev. Dis. 2016, 3, 19.

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