dc.contributor.author | Xiao, Feng | |
dc.contributor.author | Nguyen, Ngoc Uyen Nhi | |
dc.contributor.author | Wang, Ping | |
dc.contributor.author | Li, Shujuan | |
dc.contributor.author | Hsu, Ching-Cheng | |
dc.contributor.author | Thet, Suwannee | |
dc.contributor.author | Kimura, Wataru | |
dc.contributor.author | Luo, Xiang | |
dc.contributor.author | Lam, Nicholas T | |
dc.contributor.author | Menendez-Montes, Ivan | |
dc.contributor.author | Elhelaly, Waleed | |
dc.contributor.author | Cardoso, Alisson Campos | |
dc.contributor.author | Pereira, Ana Helena Macedo | |
dc.contributor.author | Singh, Rohit | |
dc.contributor.author | Sadayappan, Sakthivel | |
dc.contributor.author | Kanchwala, Mohammed | |
dc.contributor.author | Xing, Chao | |
dc.contributor.author | Ladha, Feria A | |
dc.contributor.author | Hinson, J Travis | |
dc.contributor.author | Hajjar, Roger J | |
dc.contributor.author | Hill, Joseph A | |
dc.contributor.author | Sadek, Hesham A | |
dc.date.accessioned | 2024-07-03T10:42:36Z | |
dc.date.available | 2024-07-03T10:42:36Z | |
dc.date.issued | 2024-05-06 | |
dc.identifier.citation | Circulation. 2024 May 6. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19935 | |
dc.description.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. | es_ES |
dc.description.sponsorship | This work was supported by grants from the National Institutes of Health
(R01_HL137415, R01_HL147276, R01_HL1491371, P01_HL160476-01A1,
R35_HL166563-01, P01_HL160488 [H.A.S.]; R01_HL128215, R01_
HL147933, R01_HL155765, R01_HL164586 [J.A.H.]; R01_HL105826,
R01_AR078001, R38_HL155775 [S.S.]; R01_HL165220, and R01_
HL142787 [J.T.S]); the American Heart Association (AHA_856552,
AHA_19POST34450039 [N.U.N.N.]; AHA_903385 [I.M.M.]; AHA_SURF
25UFEL34380251, and AHA_TPA 945748 [S.S.]); the Leducq Transatlantic
Network of Excellence (H.A.S.); the Hamon Center for Regenerative Science and
Medicine (H.A.S.); and an Amgen Post-Doctoral fellowship (R.S.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Lippincott Williams & Wilkins (LWW) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38708635 | es_ES |
dc.identifier.doi | 10.1161/CIRCULATIONAHA.122.059102 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | es_ES |
dc.contributor.funder | American Heart Association | es_ES |
dc.contributor.funder | Fondation Leducq | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1524-4539 | es_ES |
dc.relation.publisherversion | 10.1161/CIRCULATIONAHA.122.059102 | es_ES |
dc.identifier.journal | Circulation | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Regeneración del miocardio mediante la regulación del ciclo celular en cardiomiocitos | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |