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bioRxiv · 10.1101/2020.12.24.424022

Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis

Xiao, F.·Lam, N.·Wang, P.·Li, S.·Canseco, D.·Kimura, W.·Luo, X.·Nguyen, N. U. N.·El Helaly, W.·Singh, R.·Sadayappan, S.·Kanchwala, M.·Xing, C.·Hajjar, R.·Hill, J.·Sadek, H.
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Abstract

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.

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Xiao, F., Lam, N., Wang, P., Li, S., Canseco, D., Kimura, W., Luo, X., Nguyen, N. U. N., El Helaly, W., Singh, R., Sadayappan, S., Kanchwala, M., Xing, C., Hajjar, R., Hill, J., Sadek, H.. 2020-12-24. Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis. https://doi.org/10.1101/2020.12.24.424022

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