2026-06-14T03:33:47Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/199352024-07-04T01:01:30Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Xiao, Feng author Nguyen, Ngoc Uyen Nhi author Wang, Ping author Li, Shujuan author Hsu, Ching-Cheng author Thet, Suwannee author Kimura, Wataru author Luo, Xiang author Lam, Nicholas T author Menendez-Montes, Ivan author Elhelaly, Waleed author Cardoso, Alisson Campos author Pereira, Ana Helena Macedo author Singh, Rohit author Sadayappan, Sakthivel author Kanchwala, Mohammed author Xing, Chao author Ladha, Feria A author Hinson, J Travis author Hajjar, Roger J author Hill, Joseph A author Sadek, Hesham A author 2024-05-06 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 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. Circulation. 2024 May 6. 10.1161/CIRCULATIONAHA.122.059102 1524-4539 Circulation 38708635 http://hdl.handle.net/20.500.12105/19935 Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis.