ハナシマ　アキラ   Akira Hanashima   花島　章    所属   川崎医科大学  医学部 基礎医学　生理学1    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	CCDC141 is a Connectin/Titin and Nesprin-1 binding protein that adapts cardiomyocytes to mechanical stress.
掲載誌名	正式名：Communications biology 略　 称：Commun Biol ISSNコード：23993642/23993642
掲載区分	国外
巻・号・頁	8(1),pp.1693
著者・共著者	Akira Hanashima, Misaki Kimoto, Yoshihiro Ujihara, Ken Hashimoto, Yuu Usui, Momoko Ohira, Masato Hoshino, Kentaro Uesugi, Stephanie Witt, Dittmar Labeit, Sumiko Kimura, Takashi Murayama, Takashi Sakurai, Siegfried Labeit, Satoshi Mohri
担当区分	筆頭著者,責任著者
発行年月	2025/11
概要	The heart adapts to mechanical stresses such as hypertension, yet the underlying mechanisms remain poorly understood. We identify CCDC141 as a mechanoadaptive factor in cardiomyocytes. CCDC141 interacts with the sarcomeric connectin/titin filament system and the nuclear envelope protein nesprin-1, and localizes to the costameres in adult cardiomyocytes. CCDC141-KO mouse cardiomyocytes exhibit hypertrophy. Their mitochondria display abnormal alignment and fusion, are burdened by elevated ATP production, and show reduced spare respiratory capacity. Increased SERCA2a expression enhances Ca²⁺ handling within the sarcoplasmic reticulum of CCDC141-KO cardiomyocytes. During pressure overload-induced heart failure in mice, CCDC141 relocalizes to the nuclear envelope, suggesting a stress-responsive role in maintaining nuclear integrity. CCDC141-KO hearts show low tolerance to mechanical stress, and despite only moderate pressure overload induced by transverse aortic constriction, they are more susceptible to fatal arrhythmias and progressive heart failure with disrupted nuclear morphology. These findings provide new insights into the molecular basis of cardiac mechanoadaptation and disease.
DOI	10.1038/s42003-025-09093-6
PMID	41298937