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The sarcoplasmic reticulum is a network of tubules and cisternae localized in close association with the contractile apparatus, and regulates Ca(2+)dynamics within striated muscle cell. The sarcoplasmic reticulum maintains its shape and organization despite repeated muscle cell contractions, through mechanisms which are still under investigation. The ESCRT complexes are essential to organize membrane subdomains and modify membrane topology in multiple cellular processes. Here, we report for the first time that ESCRT-II proteins play a role in the maintenance of sarcoplasmic reticulum integrity inC. elegans ESCRT-II proteins colocalize with the sarcoplasmic reticulum marker ryanodine receptor UNC-68. The localization at the sarcoplasmic reticulum of ESCRT-II and UNC-68 are mutually dependent. Furthermore, the characterization of ESCRT-II mutants revealed a fragmentation of the sarcoplasmic reticulum network, associated with an alteration of Ca(2+)dynamics. Our data provide evidence that ESCRT-II proteins are involved in sarcoplasmic reticulum shaping.
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http://dx.doi.org/10.1242/jcs.178467 | DOI Listing |
Circ Res
September 2025
Division of Molecular Cardiovascular Biology, The Heart Institute, Cincinnati Children's Hospital Medical Center, OH. (O.B.-E., Y.K., A.M.G., K.R.H., M.L.K., J.P.V., N.S.B., J.H., J.D.M., C.A.M.).
Background: Calcium (Ca) dysregulation is a hallmark of heart failure, impairing excitation-contraction coupling and contributing to pathological remodeling. The SERCA2a (sarco/endoplasmic reticulum Ca ATPase isoform 2a) mediates Ca reuptake into the sarcoplasmic reticulum (SR) during diastole, but its activity declines in failing hearts. DWORF (dwarf open reading frame), a newly identified cardiac microprotein, enhances SERCA2a activity and improves cardiomyocyte Ca cycling and contractility.
View Article and Find Full Text PDFNat Cardiovasc Res
September 2025
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA.
Sarcoplasmic/endoplasmic reticulum (SR/ER) Ca ATPase 2a (SERCA2a) mediates Ca reuptake into the SR in cardiomyocytes. The inactivation or downregulation of SERCA2a leads to reduced contractility in the failing heart. Here we show that SERCA2a is regulated by p22, a heterodimeric partner of NADPH oxidases.
View Article and Find Full Text PDFNat Commun
August 2025
Department of Cardiology, Laboratory of Heart Center, Heart Center, Center for Translational Medicine Research, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Vascular calcification, a key risk factor for cardiovascular diseases, is driven by the phenotypic transition of vascular smooth muscle cells from a contractile to an osteogenic phenotype. NEXN, a protein highly associated with heart function, has also been implicated as a potential susceptibility factor in the development of coronary artery disease, but its role in the progression of vascular calcification remains unclear. In this study, multi-transcriptomics analysis and various animal models of male mice were used to explore the cell-specific roles and molecular mechanisms of NEXN in vascular calcification.
View Article and Find Full Text PDFPhysiol Rep
August 2025
Division of Cardiovascular Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
Multiple epidemiological studies link cardiac dysfunction with increased levels of air pollution. While cellular mechanisms underlying such dysfunction are yet to be fully elucidated, a proposed mediator of this effect is phenanthrene, a 3-ringed polycyclic aromatic hydrocarbon (PAH). Here, we used ventricular myocytes freshly isolated from healthy female sheep (Ovis aries) to study the impact of acute phenanthrene exposure on cardiac electrophysiology and intracellular Ca cycling in a large mammalian model.
View Article and Find Full Text PDFCirc Res
August 2025
Department of Physiology and Heart Otago, University of Otago, Dunedin, New Zealand (A.M.K., P.P.J.).
Calcium release through the cardiac RyR2 (type-2 ryanodine receptor) is essential for cardiac contraction. RyR2 dysfunction is associated with a spectrum of cardiac pathologies, most notably arrhythmias. While excessive RyR2 activity was historically seen as the driver of arrhythmia, it is now clear that inadequate calcium release is equally detrimental.
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