Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/19935
Title
Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis.
Author(s)
Xiao, Feng | Nguyen, Ngoc Uyen Nhi | Wang, Ping | Li, Shujuan | Hsu, Ching-Cheng | Thet, Suwannee | Kimura, Wataru | Luo, Xiang | Lam, Nicholas T | Menendez-Montes, Ivan | Elhelaly, Waleed | Cardoso, Alisson Campos | Pereira, Ana Helena Macedo | Singh, Rohit | Sadayappan, Sakthivel | Kanchwala, Mohammed | Xing, Chao | Ladha, Feria A | Hinson, J Travis | Hajjar, Roger J | Hill, Joseph A | Sadek, Hesham A
Date issued
2024-05-06
Citation
Circulation. 2024 May 6.
Language
Inglés
Document type
journal article
Abstract
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.
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