Brotto Marco A P, Nagaraj Ramakrishnan Y, Brotto Leticia S, Takeshima Hiroshi, Ma Jian Jie, Nosek Thomas M
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Cell Res. 2004 Oct;14(5):373-8. doi: 10.1038/sj.cr.7290237.
Mitsugumin 29 (MG29) is a transmembrane protein that is normally found in the triad junction of skeletal muscle. Our previous studies have shown that targeted deletion of mg29 from the skeletal muscle resulted in abnormality of the triad junction structure, and also increased susceptibility to muscle fatigue. To elucidate the basis of these effects, we investigated the properties of Ca2+-uptake and -release in toxin-skinned Extensor Digitorium Longus (EDL) muscle fibers from control and mg29 knockout mice. Compared with the control muscle, submaximal Ca2+-uptake into the sarcoplasmic reticulum (SR) was slower and the storage of Ca2+ inside the SR was less in the mutant muscle, due to increased leakage process of Ca2+ movement across the SR. The leakage pathway is associated with the increased sensitivity of Ca2+/caffeine -induced Ca2+ release to myoplasmic Ca2+. Therefore, the increased fatigability of mutant EDL muscles can result from a combination of a slowing of Ca2+ uptake, modification of Ca2+-induced Ca2+ release (CICR), and a reduction in total SR Ca2+ content.
三联体蛋白29（MG29）是一种跨膜蛋白，通常存在于骨骼肌的三联体连接处。我们之前的研究表明，从骨骼肌中靶向删除mg29会导致三联体连接结构异常，并且还会增加肌肉疲劳的易感性。为了阐明这些效应的基础，我们研究了来自对照小鼠和mg29基因敲除小鼠的毒素处理的趾长伸肌（EDL）肌纤维中Ca2+摄取和释放的特性。与对照肌肉相比，由于Ca2+跨肌浆网（SR）移动的泄漏过程增加，突变肌肉中Ca2+向肌浆网的亚最大摄取较慢，并且SR内Ca2+的储存较少。泄漏途径与Ca2+/咖啡因诱导的Ca2+释放对肌质Ca2+的敏感性增加有关。因此，突变EDL肌肉疲劳性增加可能是由于Ca2+摄取减慢、Ca2+诱导的Ca2+释放（CICR）改变以及SR中总Ca2+含量降低共同作用的结果。
