Caged Nicotinic Acid Adenine Dinucleotide Phosphate

Lee, Hon Cheung; Aarhus, Robert; Gee, Kyle R.; Kestner, Thomas A.

doi:10.1074/jbc.272.7.4172

Cited by 68 publications

(47 citation statements)

References 23 publications

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“…2a shows that a 2.5-s photolysis flash produced a rapid elevation of intracellular Ca 2ϩ , which in this particular experiment reached a height of about 1.2 arbitrary units (n ϭ 9; 0.96 Ϯ 0.19). The uncaging of NAADP ϩ had been previously shown to produce a large Ca 2ϩ transient in sea urchin eggs (19) and to activate a massive cortical exocytosis reaction (9,19,21). The Ca 2ϩ transient induced by NAADP ϩ triggered the cortical exocytosis reaction also in starfish oocytes (not shown).…”

Section: Resultsmentioning

confidence: 97%

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Nicotinic Acid Adenine Dinucleotide Phosphate-induced Ca2+ Release

Santella¹,

Kyozuka²,

Genazzani³

et al. 2000

Journal of Biological Chemistry

101

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Section: Resultsmentioning

confidence: 97%

“…The Ca 2ϩ transient induced by NAADP ϩ triggered the cortical exocytosis reaction also in starfish oocytes (not shown). Occasionally, the uncaging of NAADP ϩ in mature oocytes elicited Ca 2ϩ oscillations, as is the case in sea urchin eggs (19). Up to three Ca 2ϩ oscillations were observed over a period of 20 min (not shown).…”

Section: Resultsmentioning

confidence: 99%

Nicotinic Acid Adenine Dinucleotide Phosphate-induced Ca2+ Release

Santella¹,

Kyozuka²,

Genazzani³

et al. 2000

Journal of Biological Chemistry

101

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“…7; supplementary material Movie 1), allowing lysosomes selectively to accumulate Ca 2+ released from the ER. The reciprocal relationship is also important because in many cells NAADP-evoked Ca 2+ release from lysosomes triggers Ca 2+ release from the ER by Ca 2+ -induced Ca 2+ release via Ins(1,4,5)P 3 R (Calcraft et al, 2009) or RyR (Brailoiu et al, 2010;Cancela et al, 1999;Kinnear et al, 2008;Lee et al, 1997). Lysosome-ER junctions are reminiscent of those between mitochondria and ER (Fig.…”

Section: + Signallingmentioning

confidence: 99%

Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

López-Sanjurjo

Tovey

Prole

et al. 2013

Journal of Cell Science

126

111

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Summary Most intracellular Ca2+ signals result from opening of Ca 2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca 2+ into mitochondria. Ca 2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca 2+ signalling, but the role of lysosomal Ca 2+ uptake in Ca 2+ signalling is unexplored. Inhibition of lysosomal Ca 2+ uptake by dissipating the H + gradient (using bafilomycin A 1 ), perforating lysosomal membranes (using glycyl-Lphenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca 2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P 3 ] formation. Bafilomycin A 1 amplified the Ca 2+ signals evoked by photolysis of caged Ins(1,4,5)P 3 or by inhibition of ER Ca 2+ pumps, and it slowed recovery from them. Ca 2+ signals evoked by store-operated Ca 2+ entry were unaffected by bafilomycin A 1 . Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca 2+ released by Ins(1,4,5)P 3 receptors.

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“…Indeed, agonists and stimuli are shown to activate rapid and transient changes in NAADP levels (7,29,30), indicating the presence in cells of efficient pathways for not only the synthesis but also the degradation of NAADP. As a nucleotide, NAADP is sensitive to degradative enzymes, such as nucleotide phosphodiesterase or alkaline phosphatase (31,32). Whether these general enzymes are responsible for its degradation in cells is not known.…”

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confidence: 99%

Acidic Residues at the Active Sites of CD38 and ADP-ribosyl Cyclase Determine Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Synthesis and Hydrolysis Activities

Graeff

Liu

Kriksunov

et al. 2006

Journal of Biological Chemistry

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Nicotinic acid adenine dinucleotide phosphate (NAADP) is a novel metabolite of NADP that has now been established as a Ca 2؉ messenger in many cellular systems. Its synthesis is catalyzed by multifunctional enzymes, CD38 and ADP-ribosyl cyclase (cyclase). The degradation pathway for NAADP is unknown and no enzyme that can specifically hydrolyze it has yet been identified. Here we show that CD38 can, in fact, hydrolyze NAADP to ADP-ribose 2-phosphate. This activity was low at neutrality but greatly increased at acidic pH. This novel pH dependence suggests that the hydrolysis is determined by acidic residues at the active site. X-ray crystallography of the complex of CD38 with one of its substrates, NMN, showed that the nicotinamide moiety was in close contact with and has since been shown in a wide variety of cell types, from plants to human (reviewed in Refs. 3-5). NAADP is endogenously present in cells and its level is modulated by various agonists and stimuli, establishing its role as a second messenger (Refs. 6 and 7 and reviewed in Refs. 8 and 9). In contrast to the widespread functional activity of NAADP in cells, only two homologous proteins, mammalian CD38 and Aplysia ADP-ribosyl cyclase, have so far been identified as enzymes responsible for the synthesis of NAADP (10). CD38 is a membrane-bound protein first thought of as a lymphocyte antigen (reviewed in Refs. 11-13) but has since been found to be widely expressed in virtually all tissues examined (14 -17). It is present on the cell surface in some cases but is also localized in various intracellular organelles (15, 18 -20). The Aplysia ADP-ribosyl cyclase, on the other hand, is a soluble protein that shares about 30% sequence identity with CD38 (21) and is found in large quantities in the Aplysia ovotestis (22, 23). Both CD38 and the cyclase are novel multifunctional enzymes capable of synthesizing NAADP from NADP by catalyzing the exchange of nicotinamide in NADP with nicotinic acid (10). Both can also cyclize NAD to produce cyclic ADP-ribose (cADPR) (10, 24), another novel Ca 2ϩ messenger (reviewed in Refs. 3-5). The crystal structures of both proteins have been solved (25,26) and the catalytic glutamate residues at their enzymatic active sites identified by site-directed mutagenesis (27,28). Expectedly, a large degree of structural homology is observed between them (26).As a second messenger, NAADP levels in cells are expected to respond to physiological stimuli. Indeed, agonists and stimuli are shown to activate rapid and transient changes in NAADP levels (7,29,30), indicating the presence in cells of efficient pathways for not only the synthesis but also the degradation of NAADP. As a nucleotide, NAADP is sensitive to degradative enzymes, such as nucleotide phosphodiesterase or alkaline phosphatase (31,32). Whether these general enzymes are responsible for its degradation in cells is not known. NAADP is insensitive to regular NADase (32), and so far, no enzyme has yet been identified that can specifically hydrolyze NAADP. Here we show, unexpectedl...

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Caged Nicotinic Acid Adenine Dinucleotide Phosphate

Cited by 68 publications

References 23 publications

Nicotinic Acid Adenine Dinucleotide Phosphate-induced Ca2+ Release

Nicotinic Acid Adenine Dinucleotide Phosphate-induced Ca2+ Release

Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

Acidic Residues at the Active Sites of CD38 and ADP-ribosyl Cyclase Determine Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Synthesis and Hydrolysis Activities

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