Calcineurin controls the transcription of Na+/Ca2+ exchanger isoforms in developing cerebellar neurons
Calcineurin controls the transcription of Na+/Ca2+ exchanger isoforms in developing cerebellar neurons
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DOI：
10.1074/jbc.m000995200
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发表时间：
2000-07-07
影响因子：
4.8
通讯作者：
Carafoli, E
中科院分区：
文献类型：
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作者：
Li, L;Guerin, D;Carafoli, E
Na+/Ca2+ 交换器 (NCX) 和质膜 Ca2+-ATP 酶将 Ca2+ 从细胞质输送到细胞外空间。三个 NCX 基因（NCX1、NCX2 和 NCX3）编码具有非常相似特性的蛋白质，在组织中以不同水平表达。本质上，没有关于调节其表达的机制的信息。制备了特异性抗体并用于探讨NCX1和NCX2在大鼠小脑中的表达。 NCX2 的表达在发育过程中强烈上调，而 NCX1 的影响相对较小。在生理浓度的钾诱导成熟的培养颗粒细胞中也观察到了这一点。相比之下，较高的 K+ 浓度会诱导质膜部分去极化并促进 Ca2+ 流入，导致 NCX2 完全消失。逆转录聚合酶链反应分析表明，该过程发生在转录水平，并依赖于 Ca2+ 钙调蛋白依赖性蛋白磷酸酶（钙调神经磷酸酶）的激活。 NCX1和NCX3基因也受到去极化处理的影响：后者的转录上调，而前者剪接变体的表达模式发生改变。对 NCX1 和 NCX3 基因的影响与钙调神经磷酸酶无关。
The Na+/Ca2+ exchanger (NCX) and the plasma membrane Ca2+-ATPase export Ca2+ from the cytosol to the extracellular space. Three NCX genes (NCX1, NCX2, and NCX3), encoding proteins with very similar properties, are expressed at different levels in tissues. Essentially, no information is available on the mechanisms that regulate their expression. Specific antibodies have been prepared and used to explore the expression of NCX1 and NCX2 in rat cerebellum. The expression of NCX2 became strongly up-regulated during development, whereas comparatively minor effects were seen for NCX1. This was also observed in cultured granule cells induced to mature in physiological concentrations of potassium. By contrast, higher K+ concentrations, which induce partial depolarization of the plasma membrane and promote the influx of Ca2+, caused the complete disappearance of NCX2, Reverse transcription-polymerase chain reaction analysis showed that the process occurred at the transcriptional level and depended on the activation of the Ca2+ calmodulin-dependent protein phosphatase, calcineurin. The NCX1 and NCX3 genes were also affected by the depolarizing treatment: the transcription of the latter became upregulated, and the pattern of expression of the splice variants of the former changed. The effects on the NCX1 and NCX3 genes were calcineurin-independent.