Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient

Masaya Shimojima, Shinsuke Yuasa, Chikaaki Motoda, Gakuto Yozu, Toshihiro Nagai, Shogo Ito, Mark Lachmann, Shin Kashimura, Makoto Takei, Dai Kusumoto, Akira Kunitomi, Nozomi Hayashiji, Tomohisa Seki, Shugo Tohyama, Hisayuki Hashimoto, Masaki Kodaira, Toru Egashira, Kenshi Hayashi, Chiaki Nakanishi, Kenji SakataMasakazu Yamagishi, Keiichi Fukuda

研究成果: Article

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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.

元の言語English
記事番号44312
ジャーナルScientific reports
7
DOI
出版物ステータスPublished - 2017 3 14

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    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., ... Fukuda, K. (2017). Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient. Scientific reports, 7, [44312]. https://doi.org/10.1038/srep44312