Human Golgi antiapoptotic protein modulates intracellular calcium fluxes.
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de Mattia F, Gubser C, van Dommelen MM, Visch HJ, Distelmaier F, Postigo A, Luyten T, Parys JB, de Smedt H, Smith GL, Willems PH, van Kuppeveld FJ
Human Golgi antiapoptotic protein modulates intracellular calcium fluxes.
Mol Biol Cell. 2009 Aug;20(16):3638-45. doi: 10.1091/mbc.E09-05-0385. Epub 2009 Jun 24.
- PubMed ID
- 19553469 [ View in PubMed]
- Abstract
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 Ca(2+) homeostasis play an important role in determining cell sensitivity to apoptosis, we investigated if GAAP affected Ca(2+) signaling. Overexpression of human (h)-GAAP suppressed staurosporine-induced, capacitative Ca(2+) influx from the extracellular space. In addition, it reduced histamine-induced Ca(2+) release from intracellular stores through inositol trisphosphate receptors. h-GAAP not only decreased the magnitude of the histamine-induced Ca(2+) fluxes from stores to cytosol and mitochondrial matrices, but it also reduced the induction and frequency of oscillatory changes in cytosolic Ca(2+). Overexpression of h-GAAP lowered the Ca(2+) content of the intracellular stores and decreased the efficacy of IP(3), 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 Ca(2+) fluxes induced by both physiological and apoptotic stimuli.