Ebert, Antje Dagmar

[["dc.bibliographiccitation.artnumber","209"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Dai, Yuanyuan"],["dc.contributor.author","Amenov, Asset"],["dc.contributor.author","Ignatyeva, Nadezda"],["dc.contributor.author","Koschinski, Andreas"],["dc.contributor.author","Xu, Hang"],["dc.contributor.author","Soong, Poh Loong"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Zaccolo, Manuela"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Ebert, Antje"],["dc.date.accessioned","2020-04-14T14:41:47Z"],["dc.date.available","2020-04-14T14:41:47Z"],["dc.date.issued","2020"],["dc.description.abstract","The sarcomeric troponin-tropomyosin complex is a critical mediator of excitation-contraction coupling, sarcomeric stability and force generation. We previously reported that induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from patients with a dilated cardiomyopathy (DCM) mutation, troponin T (TnT)-R173W, display sarcomere protein misalignment and impaired contractility. Yet it is not known how TnT mutation causes dysfunction of sarcomere microdomains and how these events contribute to misalignment of sarcomeric proteins in presence of DCM TnT-R173W. Using a human iPSC-CM model combined with CRISPR/Cas9-engineered isogenic controls, we uncovered that TnT-R173W destabilizes molecular interactions of troponin with tropomyosin, and limits binding of PKA to local sarcomere microdomains. This attenuates troponin phosphorylation and dysregulates local sarcomeric microdomains in DCM iPSC-CMs. Disrupted microdomain signaling impairs MYH7-mediated, AMPK-dependent sarcomere-cytoskeleton filament interactions and plasma membrane attachment. Small molecule-based activation of AMPK can restore TnT microdomain interactions, and partially recovers sarcomere protein misalignment as well as impaired contractility in DCM TnT-R173W iPSC-CMs. Our findings suggest a novel therapeutic direction targeting sarcomere- cytoskeleton interactions to induce sarcomere re-organization and contractile recovery in DCM."],["dc.identifier.doi","10.1038/s41598-019-56597-3"],["dc.identifier.pmid","31937807"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/64087"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/336"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A12: Alternative molekulare Signaltransduktionswege durch Kardiomyopathie-verursachende Troponin-Mutationen"],["dc.relation.issn","2045-2322"],["dc.relation.workinggroup","RG Ebert (Cardiovascular Cell Biology and Systems Medicine)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY 4.0"],["dc.title","Troponin destabilization impairs sarcomere-cytoskeleton interactions in iPSC-derived cardiomyocytes from dilated cardiomyopathy patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

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[["dc.bibliographiccitation.firstpage","90"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","103"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Ebert, Antje"],["dc.contributor.author","Joshi, Amit U."],["dc.contributor.author","Andorf, Sandra"],["dc.contributor.author","Dai, Yuanyuan"],["dc.contributor.author","Sampathkumar, Shrivatsan"],["dc.contributor.author","Chen, Haodong"],["dc.contributor.author","Li, Yingxin"],["dc.contributor.author","Garg, Priyanka"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Mochly-Rosen, Daria"],["dc.contributor.author","Wu, Joseph C."],["dc.date.accessioned","2020-12-10T18:38:00Z"],["dc.date.available","2020-12-10T18:38:00Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1161/CIRCRESAHA.118.313973"],["dc.identifier.pmid","31104567"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77161"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/268"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A12: Alternative molekulare Signaltransduktionswege durch Kardiomyopathie-verursachende Troponin-Mutationen"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation.workinggroup","RG Ebert (Cardiovascular Cell Biology and Systems Medicine)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.title","Proteasome-Dependent Regulation of Distinct Metabolic States During Long-Term Culture of Human iPSC-Derived Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]