Ca2+ signals, which facilitate pluripotent changes in cell fate, reflect the balance between cation entry and export. We found that overexpression of either isoform of the Ca2+-extruding plasma membrane calcium ATPase 4 (PMCA4) pump in Jurkat T cells unexpectedly increased activation of the Ca2+-dependent transcription factor nuclear factor of activated T cells (NFAT). Coexpression of the endoplasmic reticulum-resident Ca2+ sensor stromal interaction molecule 1 (STIM1) with the PMCA4b splice variant further enhanced NFAT activity; however, coexpression with PMCA4a depressed NFAT. No PMCA4 splice variant dependence in STIM1 association was observed, whereas partner of STIM1 (POST) preferentially associated with PMCA4b over PMCA4a, which enhanced, rather than inhibited, PMCA4 function. A comparison of global and near-membrane cytosolic Ca2+ abundances during store-operated Ca2+ entry revealed that PMCA4 markedly depressed near-membrane Ca2+ concentrations, particularly when PMCA4b was coexpressed with STIM1. PMCA4b closely associated with both POST and the store-operated Ca2+ channel Orai1. Furthermore, POST knockdown increased the near-membrane Ca2+ concentration, inhibiting the global cytosolic Ca2+ increase. These observations reveal an unexpected role for POST in coupling PMCA4 to Orai1 to promote Ca2+ entry during T cell activation through Ca2+ disinhibition.

中文翻译：

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Ca2 +出口泵PMCA清除近膜Ca2 +，以促进存储操作的Ca2 +进入和NFAT激活。

Ca 2+信号有助于细胞命运的多能变化，反映了阳离子进入和排出之间的平衡。我们发现在Jurkat T细胞中，Ca2 +挤压质膜钙ATPase 4（PMCA4）泵的任何一种亚型的过表达意外地增加了活化T细胞（NFAT）的Ca2 +依赖性转录因子核因子的活化。内质网驻留Ca2 +传感器基质相互作用分子1（STIM1）与PMCA4b剪接变体的共表达进一步增强了NFAT活性；然而，与PMCA4a的共表达抑制了NFAT。在STIM1关联中未观察到PMCA4剪接变体依赖性，而STIM1（POST）的伴侣优先与PMCA4b关联，而不是PMCA4a，后者可增强而不是抑制PMCA4功能。在存储操作的Ca2 +进入过程中，全局和近膜胞质Ca2 +丰度的比较显示，PMCA4显着降低了近膜Ca2 +的浓度，特别是当PMCA4b与STIM1共表达时。PMCA4b与POST和商店操作的Ca2 +通道Orai1都紧密相关。此外，POST敲低增加了近膜Ca2 +的浓度，抑制了整体胞质Ca2 +的增加。这些观察结果揭示了POST在将PMCA4与Orai1偶联以通过Ca2 +抑制作用激活T细胞过程中促进Ca2 +进入方面出乎意料的作用。POST敲低增加了近膜Ca2 +的浓度，抑制了整体胞质Ca2 +的增加。这些观察结果揭示了POST在将PMCA4与Orai1偶联以通过Ca2 +抑制作用激活T细胞过程中促进Ca2 +进入方面出乎意料的作用。POST敲低增加了近膜Ca2 +的浓度，抑制了整体胞质Ca2 +的增加。这些观察结果揭示了POST在将PMCA4与Orai1偶联以通过Ca2 +抑制作用激活T细胞过程中促进Ca2 +进入方面出乎意料的作用。