气候变化领域集成服务门户(CCPortal): Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis

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DOI	10.1073/pnas.2025333118
	Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis
	Yang L.; Li R.-C.; Xiang B.; Li Y.-C.; Wang L.-P.; Guo Y.-B.; Liang J.-H.; Wang X.-T.; Hou T.; Xing X.; Zhou Z.-Q.; Ye H.; Feng R.-Q.; Lakatta E.G.; Chai Z.; Wang S.-Q.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC- RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Calcium signal; Coupling; Excitation-contraction; Hibernation; Ion channel
语种	英语
scopus关键词	calcium ion; caveolin 3; myocardin; protein junctophilin 2; sarcoplasmic reticulum calcium transporting adenosine triphosphatase; serum response factor; unclassified drug; adult; animal cell; animal tissue; Article; calcium overload; cardiac muscle cell; comparative study; controlled study; down regulation; enzyme regulation; heart contraction; heart failure; hibernation; intoxication; nonhuman; priority journal; protein expression; protein protein interaction; risk factor; Sciuridae; signal transduction; survival factor; transcription regulation; transmission electron microscopy; upregulation; whole cell patch clamp
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180000
作者单位	State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871, China; College of Life Science, Shenyang Normal University, Shenyang, 110034, China; Beijing Key Laboratory of Neural Regeneration and Repair, Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China; Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, MD 21224, United States; Chinese Institute for Brain Research, Beijing, 102206, China
推荐引用方式 GB/T 7714	Yang L.,Li R.-C.,Xiang B.,et al. Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis[J],2021,118(14).
APA	Yang L..,Li R.-C..,Xiang B..,Li Y.-C..,Wang L.-P..,...&Wang S.-Q..(2021).Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Yang L.,et al."Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).