Changes in plasma membrane Ca-ATPase and stromal interacting molecule 1 expression levels for Ca2+ signaling in dystrophic mdx mouse muscle
Changes in plasma membrane Ca-ATPase and stromal interacting molecule 1 expression levels for Ca2+ signaling in dystrophic mdx mouse muscle
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DOI：
10.1152/ajpcell.00144.2012
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发表时间：
2012-09-01
影响因子：
5.5
通讯作者：
Launikonis, Bradley S.
中科院分区：
文献类型：
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作者：
Cully, Tanya R.;Edwards, Joshua N.;Launikonis, Bradley S.
Cully TR、Edwards JN、Friedrich O、Stephenson DG、Murphy RM、Launikonis BS。营养不良 mdx 小鼠肌肉中 Ca2+ 信号传导的质膜 Ca-ATP 酶和基质相互作用分子 1 表达水平的变化。 Am J Physiol Cell Physiol 303：C567-C576，2012。首次发表于 2012 年 7 月 11 日； doi:10.1152/ajpcell.00144.2012.-大部分骨骼肌质膜作为管状 (t-) 系统的一部分内化，与整个肌纤维的肌浆网 (SR) 膜形成固定连接。这种安排不仅有利于从 SR 快速大量释放 Ca2+，以在纤维激发时收缩，而且对其他相互依赖的 Ca2+ 细胞调节因子也有直接影响。 SR Ca2+ 释放后，t 系统质膜 Ca-ATP 酶 (PMCA) 和钙库操纵的 Ca2+ 进入 (SOCE) 也可被激活。在肌肉中，负责快速激活 SOCE 的 SR Ca2+ 传感器似乎是 STIM1 蛋白的基质相互作用分子 1L (STIM1L) 亚型，它直接与 t 系统中的 Orai1 Ca2+ 通道相互作用。 STIM1 的常见亚型是 STIM1S，并且已表明 STIM1 与 Orai1 一起与 STIM 的伴侣蛋白 (POST) 形成复合物，从而降低 PMCA 的活性。我们之前已经表明Orai1和STIM1在营养不良的mdx小鼠肌肉中上调，在这里我们表明STIM1L和PMCA在mdx肌肉中也上调。此外，我们发现野生型（WT）和 mdx 肌肉中 STIM1L 与 STIM1S 的比例没有不同。我们还发现，与 WT 肌肉相比，mdx 中存在更大的储存依赖性 Ca2+ 流入，SR Ca2+ 释放水平相似，同时保持正常的激活和失活特性。有趣的是，尽管 PMCA 密度不同，但发现 WT 和 mdx 肌肉通过 PMCA 排出 Ca2+ 的纤维平均能力是相同的。这表明 mdx 肌肉中的 PMCA、STIM1L、STIM1S、Orai1 以及 POST 表达之间存在密切关系，以维持与 WT 肌肉中相同的 Ca2+ 挤出特性。
Cully TR, Edwards JN, Friedrich O, Stephenson DG, Murphy RM, Launikonis BS. Changes in plasma membrane Ca-ATPase and stromal interacting molecule 1 expression levels for Ca2+ signaling in dystrophic mdx mouse muscle. Am J Physiol Cell Physiol 303: C567-C576, 2012. First published July 11, 2012; doi:10.1152/ajpcell.00144.2012.-The majority of the skeletal muscle plasma membrane is internalized as part of the tubular (t-) system, forming a standing junction with the sarcoplasmic reticulum (SR) membrane throughout the muscle fiber. This arrangement facilitates not only a rapid and large release of Ca2+ from the SR for contraction upon excitation of the fiber, but has also direct implications for other interdependent cellular regulators of Ca2+. The t-system plasma membrane Ca-ATPase (PMCA) and store-operated Ca2+ entry (SOCE) can also be activated upon release of SR Ca2+. In muscle, the SR Ca2+ sensor responsible for rapidly activated SOCE appears to be the stromal interacting molecule 1L (STIM1L) isoform of STIM1 protein, which directly interacts with the Orai1 Ca2+ channel in the t-system. The common isoform of STIM1 is STIM1S, and it has been shown that STIM1 together with Orai1 in a complex with the partner protein of STIM (POST) reduces the activity of the PMCA. We have previously shown that Orai1 and STIM1 are upregulated in dystrophic mdx mouse muscle, and here we show that STIM1L and PMCA are also upregulated in mdx muscle. Moreover, we show that the ratios of STIM1L to STIM1S in wild-type (WT) and mdx muscle are not different. We also show a greater store-dependent Ca2+ influx in mdx compared with WT muscle for similar levels of SR Ca2+ release while normal activation and deactivation properties were maintained. Interestingly, the fiber-averaged ability of WT and mdx muscle to extrude Ca2+ via PMCA was found to be the same despite differences in PMCA densities. This suggests that there is a close relationship among PMCA, STIM1L, STIM1S, Orai1, and also POST expression in mdx muscle to maintain the same Ca2+ extrusion properties as in the WT muscle.