Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle
Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle
复制标题
人类和斑马鱼肌肉中兰尼碱受体钙释放通道活性需要硒蛋白 N
DOI：
10.1073/pnas.0806015105
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发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Grunwald, David Jonah
中科院分区：
文献类型：
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作者：
Jurynec, Michael J.;Xia, Ruohong;Grunwald, David Jonah
突变影响看似无关的基因产物SepN1(功能未知的硒蛋白)和RyR1(兰尼定受体细胞内钙释放通道的主要成分)，导致先天性肌病的重叠谱。为了确定SEPN和RyR在体内的直接发育和分子作用，我们分析了斑马鱼胚胎的功能丧失效应。这些研究表明，这两种蛋白质是相同的细胞分化活动所必需的，也是胚胎正常钙流动所必需的。SEPN在物理上与RyR相关，并作为RyR通道的调节器发挥作用。在没有SEPN的情况下，斑马鱼胚胎或人类患病肌肉中的兰尼定受体改变了生化特性，失去了对氧化还原条件的正常敏感性，这可能解释了为什么影响这两个因素的突变会导致类似的疾病。
Mutations affecting the seemingly unrelated gene products, SepN1, a selenoprotein of unknown function, and RyR1, the major component of the ryanodine receptor intracellular calcium release channel, result in an overlapping spectrum of congenital myopathies. To identify the immediate developmental and molecular roles of SepN and RyR in vivo, loss-of-function effects were analyzed in the zebrafish embryo. These studies demonstrate the two proteins are required for the same cellular differentiation events and are needed for normal calcium fluxes in the embryo. SepN is physically associated with RyRs and functions as a modifier of the RyR channel. In the absence of SepN, ryanodine receptors from zebrafish embryos or human diseased muscle have altered biochemical properties and have lost their normal sensitivity to redox conditions, which likely accounts for why mutations affecting either factor lead to similar diseases.