Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 282, Issue 26, Pages 18864-18871Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M610925200
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The target calcium store of nicotinic acid adenine dinucleotide phosphate ( NAADP), the most potent endogenous calcium-mobilizing compound known to date, has been proposed to reside in the lysosomal compartment or in the endo/sarcoplasmic reticulum. This study was performed to test the hypothesis of a lysosomal versus an endoplasmic reticular calcium store sensitive to NAADP in T-lymphocytes. Pretreatment of intact Jurkat T cells with glycyl-phenylalanine 2-naphthylamide largely reduced staining of lysosomes by LysoTracker Red and abolished NAADP-induced Ca2+ signaling. However, the inhibitory effect was not specific since Ca2+ mobilization by D-myoinositol 1,4,5-trisphosphate and cyclic ADP-ribose was abolished, too. Bafilomycin A1, an inhibitor of the lysosomal H+-ATPase, did not block or reduce NAADP-induced Ca2+ signaling, although it effectively prevented labeling of lysosomes by LysoTracker Red. Further, previous T cell receptor/CD3 stimulation in the presence of bafilomycin A1, assumed to block refilling of lysosomal Ca2+ stores, did not antagonize subsequent NAADP-induced Ca2+ signaling. In contrast to bafilomycin A1, emptying of the endoplasmic reticulum by thapsigargin almost completely prevented Ca2+ signaling induced by NAADP. In conclusion, in T-lymphocytes, no evidence for involvement of lysosomes in NAADP-mediated Ca2+ signaling was obtained. The sensitivity of NAADP-induced Ca2+ signaling toward thapsigargin, combined with our recent results identifying ryanodine receptors as the target calcium channel of NAADP (Dammermann, W., and Guse, A. H. (2005) J. Biol. Chem. 280, 21394 - 21399), rather suggest that the target calcium store of NAADP in T cells is the endoplasmic reticulum.
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