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Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes

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Published in Journal of Biological Chemistry. 1997, vol. 272, no. 45, p. 28360-28367
Abstract This study addresses the role of store-operated Ca2+ influx in the regulation of exocytosis in inflammatory cells. In HL-60 granulocytes, which do not possess voltage-operated Ca2+ channels, the chemotactic peptide fMet-Leu-Phe (fMLP) was able to stimulate store-operated Ca2+ influx and to trigger exocytosis of primary granules. An efficient triggering of exocytosis by fMLP required the presence of extracellular Ca2+ and was inhibited by blockers of store-operated Ca2+ influx. However, receptor-independent activation of store-operated Ca2+ influx through thapsigargin did not trigger exocytosis. fMLP was unable to stimulate exocytosis in the absence of cytosolic free Ca2+ concentration [Ca2+]c elevations. However, a second signal generated by fMLP synergized with store-operated Ca2+ influx to trigger exocytosis and led to a left shift of the exocytosis/[Ca2+]c relationship in ionomycin-stimulated cells. The synergistic fMLP-generated signaling cascade was long-lasting, involved a pertussis toxin-sensitive G protein and a phosphatidylinositol 3-kinase. In summary, store-operated Ca2+ influx is crucial for the efficient triggering of exocytosis in HL-60 granulocytes, but, as opposed to Ca2+ influx through voltage-operated Ca2+ channels in neurons, it is not a sufficient stimulus by itself and requires synergistic receptor-generated signals.
Keywords Androstadienes/pharmacologyCalcium/ metabolismCytoplasmic Granules/drug effects/metabolismDrug SynergismEnzyme ActivationEnzyme Inhibitors/pharmacologyEstrenes/pharmacologyExocytosis/drug effectsGTP-Binding Proteins/metabolismGenistein/pharmacologyGranulocytes/cytology/drug effects/ metabolismHL-60 CellsHumansN-Formylmethionine Leucyl-Phenylalanine/pharmacologyPertussis ToxinPhosphodiesterase Inhibitors/pharmacologyPhospholipase D/metabolismPyrrolidinones/pharmacologySignal TransductionThapsigargin/pharmacologyType C Phospholipases/antagonists & inhibitorsVirulence Factors, Bordetella/pharmacology
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PMID: 9353293
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Other version: http://www.jbc.org/content/272/45/28360.full.pdf
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NUSSE, Olivier et al. Store-operated Ca2+ influx and stimulation of exocytosis in HL-60 granulocytes. In: Journal of Biological Chemistry, 1997, vol. 272, n° 45, p. 28360-28367. https://archive-ouverte.unige.ch/unige:7449

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Deposited on : 2010-06-21

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