title: Human Golgi antiapoptotic protein modulates intracellular calcium fluxes.
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.
authors: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, The Netherlands.
authors: Fabrizio
authors: F
authors: de Mattia
authors: Caroline
authors: C
authors: Gubser
authors: Michiel M T
authors: MM
authors: van Dommelen
authors: Henk-Jan
authors: HJ
authors: Visch
authors: Felix
authors: F
authors: Distelmaier
authors: Antonio
authors: A
authors: Postigo
authors: Tomas
authors: T
authors: Luyten
authors: Jan B
authors: JB
authors: Parys
authors: Humbert
authors: H
authors: de Smedt
authors: Geoffey L
authors: GL
authors: Smith
authors: Peter H G M
authors: PH
authors: Willems
authors: Frank J M
authors: FJ
authors: van Kuppeveld
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C518281:TMBIM4 protein, human; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium