Yoshida Morikatsu, Minamisawa Susumu, Shimura Miei, Komazaki Shinji, Kume Hideaki, Zhang Miao, Matsumura Kiyoyuki, Nishi Miyuki, Saito Minori, Saeki Yasutake, Ishikawa Yoshihiro, Yanagisawa Teruyuki, Takeshima Hiroshi
Medical Chemistry and Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
J Biol Chem. 2005 Feb 4;280(5):3500-6. doi: 10.1074/jbc.M406618200. Epub 2004 Nov 29.
Sarcalumenin (SAR), specifically expressed in striated muscle cells, is a Ca2+-binding protein localized in the sarcoplasmic reticulum (SR) of the intracellular Ca2+ store. By generating SAR-deficient mice, we herein examined its physiological role. The mutant mice were apparently normal in growth, health, and reproduction, indicating that SAR is not essential for fundamental muscle functions. SAR-deficient skeletal muscle carrying irregular SR ultrastructures retained normal force generation but showed slow relaxation phases after contractions. A weakened Ca2+ uptake activity was detected in the SR prepared from mutant muscle, indicating that SAR contributes to Ca2+ buffering in the SR lumen and also to the maintenance of Ca2+ pump proteins. Cardiac myocytes from SAR-deficient mice showed slow contraction and relaxation accompanied by impaired Ca2+ transients, and the mutant mice exhibited a number of impairments in cardiac performance as determined in electrocardiography, ventricular catheterization, and echocardiography. The results obtained demonstrate that SAR plays important roles in improving the Ca2+ handling functions of the SR in striated muscle.
肌钙蛋白（SAR）特异性表达于横纹肌细胞中，是一种定位于细胞内钙库肌浆网（SR）的钙结合蛋白。通过培育缺乏SAR的小鼠，我们在此研究了其生理作用。突变小鼠在生长、健康和繁殖方面明显正常，这表明SAR对于基本的肌肉功能并非必不可少。携带不规则SR超微结构的缺乏SAR的骨骼肌保留了正常的力产生，但收缩后显示出缓慢的舒张期。在从突变肌肉制备的SR中检测到钙摄取活性减弱，这表明SAR有助于SR腔中的钙缓冲以及钙泵蛋白的维持。来自缺乏SAR的小鼠的心肌细胞表现出缓慢的收缩和舒张，并伴有钙瞬变受损，并且突变小鼠在心电图、心室导管插入术和超声心动图检查中表现出许多心脏功能障碍。所获得的结果表明，SAR在改善横纹肌中SR的钙处理功能方面发挥着重要作用。
