Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis

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. /{gamma}-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phosphoforms of -adducin in-vitro and in-vivo identified Thr445/Thr480 phosphorylation of a short isoform of adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this -adducin variant along with {gamma}-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with -actinin. These results highlight an important mechanism for coordination of cytoskeletal morphological changes during cardiomyocyte mitosis.