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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Calcineurin controls inositol 1,4,5-trisphosphate type 1 receptor expression in neurons
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Calcineurin controls inositol 1,4,5-trisphosphate type 1 receptor expression in neurons

机译：钙调神经磷酸酶控制神经元中肌醇1,4,5-三磷酸1型受体的表达

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摘要

In the central nervous system, release of Ca2+ from intracellular stores contributes to numerous functions, including neurotransmitter release and long-term potentiation and depression. We have investigated the dcvelop- mental profile and the regulation of inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) in primary cultures of cerebellar granule cells. The expression of both receptor types increases during development. Whcreas the expression of type 1 IP3R appears to be regulated by Ca2+ influx through L type channels or N-melhyl-D-aspartate (NMDA) receptors, RyR levels increase independently of Ca2+. The main target of Ca2+-influx-regulating IP3R expression is the Ca2+ calmodulin-dependent protein phosphatase calcineurin, because pharmacological blockade of this protein abolishes IP3R exprcssion. Although calcineurin has been shown to regulate the phosphorylation state of the IP3R, the effect described here is at the transcriptional level because IP3R mRNA chauges in parallel with protein levels. Thus, calcineurin plays a dual role in IP3R-mediated Ca2+ signaling: it regulates IP3R function by dephosphorylation in the short-term time scale and IP3R expression over more extended periods.
机译：在中枢神经系统中，Ca2 +从细胞内储存的释放有助于许多功能，包括神经递质的释放以及长期的增强和抑制。我们已经研究了小脑颗粒细胞原代培养物中肌醇1,4,5-三磷酸受体（IP3R）和ryanodine受体（RyR）的发育和调节。两种受体类型的表达在发育过程中增加。尽管1型IP3R的表达似乎受Ca2 +通过L型通道或N-甲基-D-天门冬氨酸（NMDA）受体的流入调节，但RyR的水平独立于Ca2 +而增加。 Ca2 +流入调节IP3R表达的主要目标是Ca2 +钙调蛋白依赖性蛋白磷酸酶钙调磷酸酶，因为该蛋白的药理学阻断作用取消了IP3R的表达。尽管已显示钙调神经磷酸酶调节IP3R的磷酸化状态，但此处描述的作用是转录水平的，因为IP3R mRNA的变化与蛋白质水平平行。因此，钙调神经磷酸酶在IP3R介导的Ca2 +信号传导中起着双重作用：它在短期内通过去磷酸化来调节IP3R的功能，并在更长的时间内表达IP3R。

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