Constanze Erdmann, Roua Hassoun, Sebastian Schmitt, Carlos Kikuti, Anne Houdusse, Antonina Joanna Mazur, Andreas Mügge, Nazha Hamdani, Matthias Geyer, Kornelia Jaquet, Hans Georg Mannherz
- The human mutant cardiac \(\alpha\)-actins p.A295S or p.R312H and p.E361G, correlated with hypertrophic or dilated cardiomyopathy, respectively, were expressed by the \(\textit {baculovirus/Sf21}\) insect cell system and purified to homogeneity. The purified cardiac actins maintained their native state but showed differences in \(Ca^{2+}\)-sensitivity to stimulate the myosin-subfragment1 ATPase. Here we analyzed the interactions of these c-actins with actin-binding and -modifying proteins implicated in cardiomyocyte differentiation. We demonstrate that Arp2/3 complex and the formin mDia3 stimulated the polymerization rate and extent of the c-actins, albeit to different degrees. In addition, we tested the effect of the MICAL-1 monooxygenase, which modifies the supramolecular actin organization during development and adaptive processes. MICAL-1 oxidized these c-actin variants and induced their de-polymerization, albeit at different rates. Transfection experiments using MDCK cells demonstrated the preferable incorporation of wild type and p.A295S c-actins into their microfilament system but of p.R312H and p.E361G actins into the submembranous actin network. Transduction of neonatal rat cardiomyocytes with adenoviral constructs coding HA-tagged c-actin variants showed their incorporation into microfilaments after one day in culture and thereafter into thin filaments of nascent sarcomeric structures at their plus ends (Z-lines) except the p.E361G mutant, which preferentially incorporated at the minus ends.
MetadatenAuthor: | Constanze ErdmannGND, Roua HassounGND, Sebastian SchmittGND, Carlos KikutiORCiDGND, Anne HoudusseGND, Antonina Joanna MazurORCiDGND, Andreas MüggeORCiDGND, Nazha HamdaniGND, Matthias GeyerORCiDGND, Kornelia JaquetGND, Hans Georg MannherzGND |
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URN: | urn:nbn:de:hbz:294-84570 |
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DOI: | https://doi.org/10.3390/antiox10071082 |
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Parent Title (English): | Antiodxidants |
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Publisher: | MDPI |
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Place of publication: | Basel |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/12/09 |
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Date of first Publication: | 2021/07/05 |
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Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
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Tag: | Open Access Fonds ATPase; Arp2/3 complex; MICAL; cardiac actin; cardiomyopathies |
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Volume: | 10 |
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Issue: | 7, Article 1082 |
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First Page: | 1082-1 |
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Last Page: | 1082-19 |
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Note: | Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum. |
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Institutes/Facilities: | Institut für Anatomie, Abteilung für Anatomie und Molekulare Embryologie |
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| St. Josef-Hospital Bochum, Medizinische Klinik II, Klinik für Kardiologie |
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| Medizinische Fakultät, Interdisziplinäres Institut für Forschung und Lehre (IFL) |
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Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
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open_access (DINI-Set): | open_access |
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faculties: | Medizinische Fakultät |
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Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |
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