2026-05-17T01:18:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/258842025-12-18T12:56:21Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Douvdevany, Guy
author
Erlich, Itai
author
Haimovich-Caspi, Lilac
author
Mashiah, Tomer
author
Prondzynski, Maksymilian
author
Pricolo, Maria Rosaria
author
Alegre-Cebollada, Jorge
author
Linke, Wolfgang A
author
Carrier, Lucie
author
Kehat, Izhak
funder
Israel Science Foundation
funder
Fondation Leducq
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2024-12-16T10:37:18Z
2024-12-16T10:37:18Z
2024-08-02
Circ Res. 2024 Aug 2;135(4):474-487.
Circulation Research
38962864
https://hdl.handle.net/20.500.12105/25884
How the sarcomeric complex is continuously turned over in long-living cardiomyocytes is unclear. According to the prevailing model of sarcomere maintenance, sarcomeres are maintained by cytoplasmic soluble protein pools with free recycling between pools and sarcomeres. We imaged and quantified the turnover of expressed and endogenous sarcomeric proteins, including the giant protein titin, in cardiomyocytes in culture and in vivo, at the single cell and at the single sarcomere level using pulse-chase labeling of Halo-tagged proteins with covalent ligands. We disprove the prevailing protein pool model and instead show an ordered mechanism in which only newly translated proteins enter the sarcomeric complex while older ones are removed and degraded. We also show that degradation is independent of protein age and that proteolytic extraction is a rate-limiting step in the turnover. We show that replacement of sarcomeric proteins occurs at a similar rate within cells and across the heart and is slower in adult cells. Our findings establish a unidirectional replacement model for cardiac sarcomeres subunit replacement and identify their turnover principles.
eng
cells, cultured
muscle proteins
myocytes, cardiac
proteostasis
sarcomeres
Imaging of Existing and Newly Translated Proteins Elucidates Mechanisms of Sarcomere Turnover.
research article
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URL
https://repisalud.isciii.es/bitstreams/f5300889-ae8f-4971-9d14-0f7893172be6/download
File
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7026355a723357060340fe7157770a07
9237246
application/pdf
Imaging of Existing_Circ Res_2024.pdf