Co-expression of MG29 and ryanodine receptor leads to apoptotic cell death -: Effect mediated by intracellular Ca2+ release
Co-expression of MG29 and ryanodine receptor leads to apoptotic cell death -: Effect mediated by intracellular Ca2+ release
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DOI：
10.1074/jbc.c400030200
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发表时间：
2004-05-07
影响因子：
4.8
通讯作者：
Ma, JJ
中科院分区：
文献类型：
--
作者：
Pan, Z;Hirata, Y;Ma, JJ
细胞内Ca~(2+)动态平衡的紊乱可以调节细胞的增殖和凋亡过程。我们前期的研究表明，MG29(mitsugumin 29，MG29)是一种突触素相关蛋白，定位于骨骼肌的三联体连接处，通过调节钙库操作的钙离子进入过程，在肌肉钙信号转导中发挥重要作用。在这里，我们报道了MG29与Ryanodine受体(RyR)/钙释放通道之间的功能相互作用。纯化的MG29蛋白增强了RyR/Ca~(2+)释放通道结合到脂质双层膜上的活性。MG29和RyR在中国仓鼠卵巢细胞中的共表达导致细胞内钙库耗尽而导致细胞死亡，尽管这两种蛋白单独表达对细胞活力没有显著影响。在瞬时表达研究中，内质网中RyR的存在导致MG29从质膜滞留到细胞内细胞器。MG29和RyR之间的这种功能相互作用可能在肌肉细胞的钙信号转导过程中具有重要意义。我们的数据还表明，细胞内钙稳态的扰动可能是启动细胞凋亡的关键信号。
Perturbation of intracellular Ca2+ homeostasis has been shown to regulate the process of cell proliferation and apoptosis. Our previous studies show that mitsugumin 29 (MG29), a synaptophysin-related protein localized in the triad junction of skeletal muscle, serves an essential role in muscle Ca2+ signaling by regulating the process of store-operated Ca2+ entry. Here we report a functional interaction between MG29 and the ryanodine receptor (RyR)/Ca2+ release channel. The purified MG29 protein enhances activity of the RyR/Ca2+ release channel incorporated into the lipid bilayer membrane. Co-expression of MG29 and RyR in Chinese hamster ovary cells leads to apoptotic cell death resulting from depletion of intracellular Ca2+ stores, despite neither protein expression alone exhibits any significant effect on cell viability. In transient expression studies, the presence of RyR in the endoplasmic reticulum leads to retention of MG29 from the plasma membrane into the intracellular organelles. This functional interaction between MG29 and RyR could have important implications in the Ca2+ signaling processes of muscle cells. Our data also show that perturbation of intracellular Ca2+ homeostasis can serve as a key signal in the initiation of apoptosis.