Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes
Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes
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DOI：
10.1091/mbc.e09-05-0385
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发表时间：
2009-08-15
影响因子：
3.3
通讯作者：
van Kuppeveld, Frank J. M.
中科院分区：
文献类型：
--
作者：
de Mattia, Fabrizio;Gubser, Caroline;van Kuppeveld, Frank J. M.
高尔基抗凋亡蛋白（GAAP）是一种新的细胞死亡调节因子，在真核生物和一些痘病毒中高度保守，但其分子机制尚不清楚。鉴于细胞内Ca2+稳态的改变在决定细胞对凋亡的敏感性方面起着重要作用，我们研究了GAAP是否影响Ca2+信号传导。human (h)-GAAP的过表达抑制了staurosporine诱导的细胞外Ca2+内流。此外，它通过肌醇三磷酸受体减少了组胺诱导的细胞内Ca2+释放。h-GAAP不仅降低了组胺诱导的Ca2+从储存到细胞质和线粒体基质的通量的大小，而且还降低了细胞质Ca2+振荡变化的诱导和频率。过表达h-GAAP降低了细胞内储存的Ca2+含量，降低了IP3的功效，为观察结果提供了可能的解释。当h-GAAP被siRNA敲除时，得到相反的效果。因此，我们的数据表明，h-GAAP调节生理和凋亡刺激诱导的细胞内Ca2+通量。
Golgi antiapoptotic protein (GAAP) is a novel regulator of cell death that is highly conserved in eukaryotes and present in some poxviruses, but its molecular mechanism is unknown. Given that alterations in intracellular Ca2+ homeostasis play an important role in determining cell sensitivity to apoptosis, we investigated if GAAP affected Ca2+ signaling. Overexpression of human (h)-GAAP suppressed staurosporine-induced, capacitative Ca2+ influx from the extracellular space. In addition, it reduced histamine-induced Ca2+ release from intracellular stores through inositol trisphosphate receptors. h-GAAP not only decreased the magnitude of the histamine-induced Ca2+ fluxes from stores to cytosol and mitochondrial matrices, but it also reduced the induction and frequency of oscillatory changes in cytosolic Ca2+. Overexpression of h-GAAP lowered the Ca2+ content of the intracellular stores and decreased the efficacy of IP3, providing possible explanations for the observed results. Opposite effects were obtained when h-GAAP was knocked down by siRNA. Thus, our data demonstrate that h-GAAP modulates intracellular Ca2+ fluxes induced by both physiological and apoptotic stimuli.