CMYA5 establishes cardiac dyad architecture and positioning.

Autor: Lu F; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA., Ma Q; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA., Xie W; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, 710049, Xi'an, Shanxi, China., Liou CL; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA., Zhang D; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.; State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, 430062, Wuhan, Hubei, China., Sweat ME; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA., Jardin BD; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA., Naya FJ; Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, MA, 02215, USA., Guo Y; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.; Peking University Health Science Center, School of Basic Medical Sciences, The Institute of Cardiovascular Sciences, Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, 100191, Beijing, China., Cheng H; State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, 100871, Beijing, China., Pu WT; Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. william.pu@cardio.chboston.org.; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA, 02138, USA. william.pu@cardio.chboston.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Apr 21; Vol. 13 (1), pp. 2185. Date of Electronic Publication: 2022 Apr 21.
DOI: 10.1038/s41467-022-29902-4
Abstrakt: Cardiac excitation-contraction coupling requires dyads, the nanoscopic microdomains formed adjacent to Z-lines by apposition of transverse tubules and junctional sarcoplasmic reticulum. Disruption of dyad architecture and function are common features of diseased cardiomyocytes. However, little is known about the mechanisms that modulate dyad organization during cardiac development, homeostasis, and disease. Here, we use proximity proteomics in intact, living hearts to identify proteins enriched near dyads. Among these proteins is CMYA5, an under-studied striated muscle protein that co-localizes with Z-lines, junctional sarcoplasmic reticulum proteins, and transverse tubules in mature cardiomyocytes. During cardiac development, CMYA5 positioning adjacent to Z-lines precedes junctional sarcoplasmic reticulum positioning or transverse tubule formation. CMYA5 ablation disrupts dyad architecture, dyad positioning at Z-lines, and junctional sarcoplasmic reticulum Ca 2+ release, leading to cardiac dysfunction and inability to tolerate pressure overload. These data provide mechanistic insights into cardiomyopathy pathogenesis by demonstrating that CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines, establishes dyad architecture, and regulates dyad Ca 2+ release.
(© 2022. The Author(s).)
Databáze: MEDLINE
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