Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.
Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.
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DOI：
10.1038/srep44312
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发表时间：
2017-03-14
影响因子：
4.6
通讯作者：
Fukuda K
中科院分区：
文献类型：
--
作者：
Shimojima M;Yuasa S;Motoda C;Yozu G;Nagai T;Ito S;Lachmann M;Kashimura S;Takei M;Kusumoto D;Kunitomi A;Hayashiji N;Seki T;Tohyama S;Hashimoto H;Kodaira M;Egashira T;Hayashi K;Nakanishi C;Sakata K;Yamagishi M;Fukuda K
细胞核钙瞬变的改变是心脏重塑的早期事件。在心肌细胞中，核内钙瞬变的调节部分独立于胞浆内钙瞬变。一种核膜蛋白Emerin由EMD编码，EMD突变导致Emery-Dreifuss肌营养不良症（EDMD）。目前还不清楚Emerin是否参与细胞核Ca 2+稳态。本研究的目的是阐明Emerin在肥大刺激的大鼠心肌细胞和EDMD诱导的多能干细胞（iPS）来源的心肌细胞的核结构和Ca 2+瞬变方面的作用。心肌肥大刺激增加核面积，减少核内陷，并增加核钙瞬变的半衰减时间在心肌细胞。Emd敲除的心肌细胞在肥大刺激后表现出类似的特性。EDMD-iPS细胞衍生的心肌细胞显示核面积增加，核内陷减少，核Ca 2+瞬变的半衰减时间增加。EDMD患者的尸检心脏也显示核面积增加和核内陷减少。这些数据表明，Emerin起着至关重要的作用，在核结构和核Ca 2+瞬变。因此，Emerin和核Ca 2+瞬变是心力衰竭和EDMD的可能治疗靶点。
Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD.