Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis.

Autor:	Xiao F; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Nguyen NUN; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Wang P; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Li S; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Hsu CC; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Thet S; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Kimura W; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Japan (W.K.)., Luo X; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Lam NT; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Menendez-Montes I; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Elhelaly WM; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Cardoso AC; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas (A.C.C., A.H.M.P.)., Pereira AHM; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas (A.C.C., A.H.M.P.)., Singh R; Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, OH (R.S., S.S.).; Amgen Research, Department of Cardiometabolic Disorders, Amgen, South San Francisco, CA (R.S.)., Sadayappan S; Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, OH (R.S., S.S.)., Kanchwala M; Eugene McDermott Center for Human Growth and Development (M.K., C.X.), University of Texas Southwestern Medical Center, Dallas., Xing C; Eugene McDermott Center for Human Growth and Development (M.K., C.X.), University of Texas Southwestern Medical Center, Dallas.; Lyda Hill Department of Bioinformatics (C.X.), University of Texas Southwestern Medical Center, Dallas.; O'Donnell School of Public Health (C.X.), University of Texas Southwestern Medical Center, Dallas., Ladha FA; University of Connecticut Health Center, Farmington (F.A.L., J.T.H.)., Hinson JT; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas.; University of Connecticut Health Center, Farmington (F.A.L., J.T.H.).; Jackson Laboratory for Genomic Medicine, Farmington, CT (J.T.H.)., Hajjar RJ; Gene & Cell Therapy Institute, Mass General Brigham, Cambridge, MA (R.J.H.)., Hill JA; Moss Heart Center (J.A.H.), University of Texas Southwestern Medical Center, Dallas.; Department of Molecular Biology (J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas., Sadek HA; Department of Internal Medicine (Cardiology) (F.X., N.U.N.N., P.W., S.L., C.-C.H., S.T., W.K., X.L., N.T.L., I.M.-M., W.M.E., A.C.C., A.H.M.P., J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Department of Molecular Biology (J.A.H., H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Department of Biophysics (H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Hamon Center for Regenerative Science and Medicine (H.A.S.), University of Texas Southwestern Medical Center, Dallas.; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain (H.A.S.).
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2024 Sep 03; Vol. 150 (10), pp. 791-805. Date of Electronic Publication: 2024 May 06.
DOI:	10.1161/CIRCULATIONAHA.122.059102
Abstrakt:	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. Competing Interests: S.S. provides consulting and collaborative research studies to the Leducq Foundation Cure Phospholamban Induced Cardiomyopathy (CURE-PLAN), Red Saree Inc, Alexion, and Affinia Therapeutics Inc, but such work is unrelated to the content of this article. The other authors report no conflicts.
Databáze:	MEDLINE
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