{"doi":"10.1161/circulationaha.122.059102","title":"Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis","abstract":"BACKGROUND: Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes. METHODS: Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo. RESULTS: We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in vitro and in vivo identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin. CONCLUSIONS: These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.","journal":"Circulation","year":2024,"id":433992,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240343,"name":"Ngoc Uyen Nhi Nguyen","orcid":"0000-0003-0694-3176","position":1,"is_corresponding":false},{"id":366084,"name":"Ping Wang","orcid":"0000-0001-7277-0520","position":2,"is_corresponding":false},{"id":366082,"name":"Shujuan Li","orcid":"0000-0003-0784-8592","position":3,"is_corresponding":false},{"id":1232394,"name":"Ching‐Cheng Hsu","orcid":"0000-0002-8804-6171","position":4,"is_corresponding":false},{"id":265324,"name":"Suwannee Thet","orcid":null,"position":5,"is_corresponding":false},{"id":626456,"name":"Wataru Kimura","orcid":"0000-0001-6548-6353","position":6,"is_corresponding":false},{"id":282882,"name":"Xiang Luo","orcid":"0000-0002-7647-6094","position":7,"is_corresponding":false},{"id":240333,"name":"Nicholas T. 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Ladha","orcid":"0000-0002-8576-3976","position":17,"is_corresponding":false},{"id":255238,"name":"J. Travis Hinson","orcid":"0000-0003-1455-113X","position":18,"is_corresponding":false},{"id":57441,"name":"Roger J. Hajjar","orcid":"0000-0003-2522-1507","position":19,"is_corresponding":false},{"id":57436,"name":"Joseph A. Hill","orcid":"0000-0002-5379-1614","position":20,"is_corresponding":false},{"id":240355,"name":"Hesham A. 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