Human golgi antiapoptotic protein modulates intracellular calcium fluxes
de Mattia, Fabrizio × Gubser, Caroline van Dommelen, Michiel M T Visch, Henk-Jan Distelmaier, Felix Postigo, Antonio Luyten, Tomas Parys, Jan De Smedt, Humbert Smith, Geoffrey L Willems, Peter H G M van Kuppeveld, Frank J M #
American Society for Cell Biology
Molecular Biology of the Cell vol:20 issue:16 pages:3638-3645
Monitoring Editor: John York Golgi anti-apoptotic 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 (IP3Rs). 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 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 Ca(2+) fluxes induced by both physiological and apoptotic stimuli.