Cardiac-specific expression of calcineurin reverses embryonic lethality in calreticulin-deficient mouse
Cardiac-specific expression of calcineurin reverses embryonic lethality in calreticulin-deficient mouse
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DOI：
10.1074/jbc.m209900200
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发表时间：
2002-12-27
影响因子：
4.8
通讯作者：
Michalak, M
中科院分区：
文献类型：
--
作者：
Guo, L;Nakamura, K;Michalak, M
钙网蛋白是一种内质网。常驻钙结合分子伴侣。由于钙网蛋白缺乏小鼠心脏发育受损而导致胚胎死亡，说明了该蛋白的重要性。这种表型背后的分子细节尚不清楚。在这项研究中，我们表明，激活的钙调磷酸酶的过度表达逆转了钙网蛋白缺乏小鼠心脏发育的缺陷，并挽救了胚胎死亡。存活小鼠心脏发育无缺陷，但表现出生长迟缓、低血糖、血清甘油三酯和胆固醇水平升高。由于钙网蛋白缺乏激活的钙调磷酸酶胚胎致死率的恢复强调了钙网蛋白-钙调磷酸酶功能对早期心脏发育过程中Ca 2+依赖性信号级联的影响。这些研究结果表明，钙网蛋白和钙调神经磷酸酶发挥重要作用的钙离子依赖性途径的正常心脏发育，并解释了钙网蛋白缺乏表型的救援的分子基础。
Calreticulin is an endoplasmic reticulum. resident Ca2+-binding chaperone. The importance of the protein is illustrated by embryonic lethality because of impaired cardiac development in calreticulin-deficient mice. The molecular details underlying this phenotype are not understood. In this study, we show that overexpression of activated calcineurin reverses the defect in cardiac development observed in calreticulin-deficient mice and rescues them from embryonic lethality. The surviving mice show no defect in cardiac development but exhibited growth retardation, hypoglycemia, increased levels of serum triacylglycerols, and cholesterol. Reversal of embryonic lethality because of calreticulin deficiency by activated calcineurin underscores the impact of the calreticulin-calcineurin functions on the Ca2+- dependent signaling cascade during early cardiac development. These findings show that calreticulin and calcineurin play fundamental roles in Ca2+-dependent pathways essential for normal cardiac development and explain the molecular basis for the rescue of calreticulin-deficient phenotype.