Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):6969-74. doi: 10.1073/pnas.1201204109. Epub 2012 Apr 16.
Stimulation of cells with physiological concentrations of calcium-mobilizing agonists often results in the generation of repetitive cytoplasmic Ca(2+) oscillations. Although oscillations arise from regenerative Ca(2+) release, they are sustained by store-operated Ca(2+) entry through Ca(2+) release-activated Ca(2+) (CRAC) channels. Here, we show that following stimulation of cysteinyl leukotriene type I receptors in rat basophilic leukemia (RBL)-1 cells, large amplitude Ca(2+) oscillations, CRAC channel activity, and downstream Ca(2+)-dependent nuclear factor of activated T cells (NFAT)-driven gene expression are all exclusively maintained by the endoplasmic reticulum Ca(2+) sensor stromal interaction molecule (STIM) 1. However, stimulation of tyrosine kinase-coupled FCεRI receptors evoked Ca(2+) oscillations and NFAT-dependent gene expression through recruitment of both STIM2 and STIM1. We conclude that different agonists activate different STIM proteins to sustain Ca(2+) signals and downstream responses.
细胞受到生理浓度的钙动员激动剂刺激后，通常会产生重复的细胞质 Ca(2+) 振荡。尽管振荡是由再生性 Ca(2+) 释放引起的，但它们通过 Ca(2+) 释放激活的 Ca(2+) (CRAC) 通道的储存操作 Ca(2+) 内流来维持。在这里，我们表明，在大鼠嗜碱性白血病 (RBL)-1 细胞中刺激半胱氨酰白三烯 I 型受体后，大振幅 Ca(2+) 振荡、CRAC 通道活性以及下游 Ca(2+) 依赖性激活 T 细胞的核因子 (NFAT)-驱动的基因表达都仅由内质网 Ca(2+) 传感器基质相互作用分子 (STIM) 1 维持。然而，通过募集 STIM2 和 STIM1，酪氨酸激酶偶联的 FCεRI 受体的刺激引发了 Ca(2+) 振荡和 NFAT 依赖性基因表达。我们得出结论，不同的激动剂激活不同的 STIM 蛋白来维持 Ca(2+) 信号和下游反应。
