{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:07Z","timestamp":1787027527345,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Deutsche Forschungsgemeinschaft (DFG)","award":["MA 807\/19-1; HA7512\/2-1; and HA 7512\/2-4"],"award-info":[{"award-number":["MA 807\/19-1; HA7512\/2-1; and HA 7512\/2-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The human mutant cardiac \u03b1-actins p.A295S or p.R312H and p.E361G, correlated with hypertrophic or dilated cardiomyopathy, respectively, were expressed by the baculovirus\/Sf21 insect cell system and purified to homogeneity. The purified cardiac actins maintained their native state but showed differences in Ca2+-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.<\/jats:p>","DOI":"10.3390\/antiox10071082","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T22:02:04Z","timestamp":1625522524000},"page":"1082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Integration of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilated Cardiomyopathy (p.R312H and p.E361G) into Cellular Structures"],"prefix":"10.3390","volume":"10","author":[{"given":"Constanze","family":"Erdmann","sequence":"first","affiliation":[{"name":"Department of Anatomy and Molecular Embryology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roua","family":"Hassoun","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, D-44780 Bochum, Germany"},{"name":"Department of Cardiology, St. Josef-Hospital and Bergmannsheil, Ruhr University Bochum, D-44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Institute of Structural Biology, University of Bonn, D-53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5928-2776","authenticated-orcid":false,"given":"Carlos","family":"Kikuti","sequence":"additional","affiliation":[{"name":"Institut Curie, Structural Motility Team, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Houdusse","sequence":"additional","affiliation":[{"name":"Institut Curie, Structural Motility Team, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-9030","authenticated-orcid":false,"given":"Antonina J.","family":"Mazur","sequence":"additional","affiliation":[{"name":"Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, Pl-50-383 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"M\u00fcgge","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, D-44780 Bochum, Germany"},{"name":"Department of Cardiology, St. Josef-Hospital and Bergmannsheil, Ruhr University Bochum, D-44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazha","family":"Hamdani","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, D-44780 Bochum, Germany"},{"name":"Department of Cardiology, St. Josef-Hospital and Bergmannsheil, Ruhr University Bochum, D-44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-5002","authenticated-orcid":false,"given":"Matthias","family":"Geyer","sequence":"additional","affiliation":[{"name":"Institute of Structural Biology, University of Bonn, D-53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Jaquet","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, D-44780 Bochum, Germany"},{"name":"Department of Cardiology, St. Josef-Hospital and Bergmannsheil, Ruhr University Bochum, D-44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Georg","family":"Mannherz","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Molecular Embryology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany"},{"name":"Institut f\u00fcr Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, D-44780 Bochum, Germany"},{"name":"Department of Cardiology, St. Josef-Hospital and Bergmannsheil, Ruhr University Bochum, D-44780 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0092-8674(01)00242-2","article-title":"The Genetic Basis for Cardiomyopathy: From Mutation Identification to Mechanistic 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