RT Journal Article SR Electronic T1 Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.24.424022 DO 10.1101/2020.12.24.424022 A1 Feng Xiao A1 Ping Wang A1 Shujuan Li A1 Suwannee Thet A1 Diana C. Canseco A1 Wataru Kimura A1 Xiang Luo A1 Ngoc Uyen Nhi Nguyen A1 Nicholas Lam A1 Waleed Elhelaly A1 Rohit Singh A1 Sakthivel Sadayappan A1 Mohammed Kanchwala A1 Chao Xing A1 Roger J. Hajjar A1 Joseph A. Hill A1 Hesham A. Sadek YR 2020 UL http://biorxiv.org/content/early/2020/12/24/2020.12.24.424022.abstract AB 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 abscission of daughter cardiomyocytes. Here 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 phosphoforms 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. These results highlight an important mechanism for coordination of cytoskeletal morphological changes during cardiomyocyte mitosis.Competing Interest StatementThe authors have declared no competing interest.