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Title: Human golgi antiapoptotic protein modulates intracellular calcium fluxes
Authors: 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 #
Issue Date: Aug-2009
Publisher: American Society for Cell Biology
Series Title: Molecular Biology of the Cell vol:20 issue:16 pages:3638-3645
Abstract: 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.
URI: 
ISSN: 1059-1524
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular and Cellular Signaling
× corresponding author
# (joint) last author

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