Abstract
The concept advanced by Berridge and colleagues that intracellular Ca2+-stores can be mobilized in an agonist-dependent and messenger (IP3)-mediated manner has put Ca2+-mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca2+-stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP3) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.
As cADPR and NAADP are structurally and functionally distinct, it is remarkable that they are synthesized by the same enzyme. They are thus fraternal twin messengers. We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and, through homology, found its mammalian homolog, CD38. Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion, susceptibility to bacterial infection, to social behavior of mice through modulating neuronal oxytocin secretion. We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis. This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.
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Streb H, Irvine R F, Berridge M J, et al. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature, 1983, 306: 67–69, 6605482, 1:CAS:528:DyaL2cXitVyltg%3D%3D
Bosanac I, Alattia J R, Mal T K, et al. Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature, 2002, 420: 696–700, 12442173, 1:CAS:528:DC%2BD38XpsVSiurs%3D
Clapper D L, Walseth T F, Dargie P J, et al. Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate. J Biol Chem, 1987, 262: 9561–9568, 3496336, 1:CAS:528:DyaL2sXkvFaisrs%3D
Lee H C, Walseth T F, Bratt G T, et al. Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+-mobilizing activity. J Biol Chem, 1989, 264: 1608–1615, 2912976, 1:CAS:528:DyaL1MXhtFShurY%3D
Clapper D L, Lee H C. Inositol trisphosphate induces Ca+2-release from non-mitochondrial stores in sea urchin egg homogenates. J Biol Chem, 1985, 260: 13947–3954, 2414285, 1:CAS:528:DyaL2MXlsFOrsb0%3D
Mazia D. The release of calcium in Arbacia eggs on fertilization. J Cell Comp, 1937, Physiol, 10: 291–304, 1:CAS:528:DyaA1cXisVyqtw%3D%3D
Lee H C, Aarhus R, Levitt D. The crystal structure of cyclic ADP-ribose. Nature Struct Biol, 1994, 1: 143–144, 7656029, 1:CAS:528:DyaK2cXlt1yhtbg%3D
Shuto S, Fukuoka M, Manikowsky A, et al. Total synthesis of cyclic ADP-carbocyclic-ribose, a stable mimic of Ca2+-mobilizing second messenger cyclic ADP-Ribose. J Am Chem Soc, 2001, 123: 8750–8759, 11535079, 1:CAS:528:DC%2BD3MXlvFynu70%3D
Potter B V L, Walseth T F. Medicinal chemistry and pharmacology of cyclic ADP-ribose. Curr Mol Med, 2004, 4: 303–312, 15101687, 1:CAS:528:DC%2BD2cXjt1Orsrs%3D
Walseth T F, Aarhus R, Zeleznikar R J Jr., et al. Determination of endogenous levels of cyclic ADP-ribose in rat tissues. Biochim Biophys Acta, 1991, 1094: 113–120, 1883849, 1:CAS:528:DyaK3MXmtVCju7o%3D
Lee H C, Aarhus R. A derivative of NADP mobilizes calcium stores insensitive to inositol trisphosphate and cyclic ADP-ribose. J Biol Chem, 1995, 270: 2152–2157, 7836444, 1:CAS:528:DyaK2MXjsV2ksb4%3D
Lam C M, Yeung P K, Lee H C, et al. Cyclic ADP-ribose links metabolism to multiple fission in the dinoflagellate Crypthecodinium cohnii. Cell Cal, 2009, 45: 346–357, 1:CAS:528:DC%2BD1MXjsFWks7w%3D
Navazio L, Bewell M A, Siddiqua A, et al. Calcium release from the endoplasmic reticulum of higher plants elicited by the NADP metabolite nicotinic acid adenine dinucleotide phosphate. Proc Natl Acad Sci USA, 2000, 97: 8693–8698, 10890899, 1:CAS:528:DC%2BD3cXlt1Gnsbw%3D
Wu Y, Kuzma J, Marechal E, et al. Abscisic acid signaling through cyclic ADP-ribose in plants. Science, 1997, 278: 2126–2130, 9405349, 1:CAS:528:DyaK1cXhvFOj
Johnson J D, Misler S. Nicotinic acid-adenine dinucleotide phosphate-sensitive calcium stores initiate insulin signaling in human beta cells. Proc Natl Acad Sci USA, 2002, 99: 14566–14571, 12381785, 1:CAS:528:DC%2BD38XosF2hsb4%3D
Podesta M, Zocchi E, Pitto A, et al. Extracellular cyclic ADP-ribose increases intracellular free calcium concentration and stimulates proliferation of human hemopoietic progenitors. FASEB J, 2000, 14: 680–690, 10744625, 1:CAS:528:DC%2BD3cXisFyhs78%3D
Lee H C. Cyclic ADP-ribose and NAADP. Structures, Metabolism and Functions. Dordrecht: Kluwer Academic Publishers, 2002
Kuroda R, Kontani K, Kanda Y, et al. Increase of cGMP, cADP-ribose and inositol 1,4,5-trisphosphate preceding Ca2+ transients in fertilization of sea urchin eggs. Dev, 2001, 128: 4405–4414, 1:CAS:528:DC%2BD3MXptVGltbc%3D
Leckie C, Empson R, Becchetti A, et al. The NO pathway acts late during the fertilization response in sea urchin eggs. J Biol Chem, 2003, 278: 12247–12254, 12540836, 1:CAS:528:DC%2BD3sXisVOntro%3D
Dargie P J, Agre M C, Lee H C. Comparison of Ca2+ mobilizing activities of cyclic ADP-ribose and inositol trisphosphate. Cell Regul, 1990, 1: 279–290, 2100201, 1:CAS:528:DyaK3cXhsFGlsrc%3D
Galione A, McDougall A, Busa W B, et al. Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs. Science, 1993, 261: 348–352, 8392748, 1:CAS:528:DyaK3sXltFeqsL0%3D
Lee H C, Aarhus R, Walseth T F. Calcium mobilization by dual receptors during fertilization of sea urchin eggs. Science, 1993, 261: 352–355, 8392749, 1:CAS:528:DyaK3sXltFeqsLo%3D
Lee H C. Calcium signaling: NAADP ascends as a new messenger. Curr Biol, 2003, 13: R186–R188, 12620209, 1:CAS:528:DC%2BD3sXhvFaitLc%3D
Lee H C. Nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated calcium signaling. J Biol Chem, 2005, 280: 33693–33696, 16076847, 1:CAS:528:DC%2BD2MXhtVKisbrE
Cancela J M. Specific Ca2+ signaling evoked by cholecystokinin and acetylcholine: The roles of NAADP, cADPR, and IP3. Annu Rev Physiol, 2001, 63: 99–117, 11181950, 1:CAS:528:DC%2BD3MXjtFKmt7Y%3D
Cancela J M, Churchill G C, Galione A. Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature, 1999, 398: 74–76, 10078532, 1:CAS:528:DyaK1MXhvFaksL8%3D
Yamasaki M, Thomas J M, Churchill G C, et al. Role of NAADP and cADPR in the induction and maintenance of agonist-evoked Ca2+ spiking in mouse pancreatic acinar cells. Curr Biol, 2005, 15: 874–878, 15886108, 1:CAS:528:DC%2BD2MXktVKqtbo%3D
Guse A H, Lee H C. NAADP: A universal Ca2+ trigger. Sci Signal, 2008, 1: re10, 18984909
Arredouani A, Evans A M, Ma J, et al. An emerging role for NAADP-mediated Ca2+ signaling in the pancreatic beta-cell. Islets, 2010, 2: 323–330, 21099331
Masgrau R, Churchill G C, Morgan A J, et al. NAADP: A new second messenger for glucose-induced Ca2+ responses in clonal pancreatic b-cells. Curr Biol, 2003, 13: 247–251, 12573222, 1:CAS:528:DC%2BD3sXhtVGmsLg%3D
Yamasaki M, Masgrau R, Morgan A J, et al. Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells. J Biol Chem, 2004, 279: 7234–7240, 14660554, 1:CAS:528:DC%2BD2cXht1Cksbc%3D
Galione A, Lee H C, Busa W B. Ca2+-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science, 1991, 253: 1143–1146, 1909457, 1:CAS:528:DyaK3MXmt1yrtr8%3D
Lee H C. Potentiation of calcium- and caffeine-induced calcium release by cyclic ADP-ribose. J Biol Chem, 1993, 268: 293–299, 8416936, 1:CAS:528:DyaK3sXisFWktr0%3D
Meszaros L G, Bak J, Chu A. Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel. Nature, 1993, 364: 76–79, 8391127, 1:CAS:528:DyaK3sXkvV2isr0%3D
Chen S R W, Li X L, Ebisawa K, et al. Functional characterization of the recombinant type 3 Ca2+ release channel (ryanodine receptor) expressed in HEK293 cells. J Biol Chem, 1997, 272: 24234–24246, 9305876, 1:CAS:528:DyaK2sXmsFamsr8%3D
Copello J A, Qi Y, Jeyakumar L H, et al. Lack of effect of cADP-ribose and NAADP on the activity of skeletal muscle and heart ryanodine receptors. Cell Cal, 2001, 30: 269–284, 1:CAS:528:DC%2BD3MXnvVelu7c%3D
Fruen B R, Mickelson J R, Shomer N H, et al. Cyclic ADP-ribose does not affect cardiac or skeletal muscle ryanodine receptors. FEBS Lett, 1994, 352: 123–126, 7925959, 1:CAS:528:DyaK2cXmsFanur8%3D
Tian C, Shao C H, Moore C J, et al. Gain of Function of cardiac ryanodine receptor in a rat model of type 1 diabetes. Cardiovasc Res, 2011, doi: 10.1093/cvr/cvr076
Lokuta A J, Darszon A, Beltran C, et al. Detection and functional characterization of ryanodine receptors from sea urchin eggs. J Physiol, 1998, 510,1: 155–164, 9625874, 1:CAS:528:DyaK1cXkvVKks7s%3D
Tang W X, Chen Y F, Zou A P, et al. Role of FKBP12.6 in cADPR-induced activation of reconstituted ryanodine receptors from arterial smooth muscle. Am J Physiol Heart Circ Physiol, 2002, 282: H1304–1310, 11893565, 1:CAS:528:DC%2BD38XivVent7k%3D
Cui Y, Galione A, Terrar D A. Effects of photoreleased cADP-ribose on calcium transients and calcium sparks in myocytes isolated from guinea-pig and rat ventricle. Biochem J, 1999, 342: 269–273, 10455010, 1:CAS:528:DyaK1MXmtFChtLg%3D
Macgregor A T, Rakovic S, Galione A, et al. Dual effects of cyclic ADP-ribose on sarcoplasmic reticulum Ca2+ release and storage in cardiac myocytes isolated from guinea-pig and rat ventricle. Cell Cal, 2007, 41: 537–546, 1:CAS:528:DC%2BD2sXkslKrtbo%3D
Zhang X, Tallini Y N, Chen Z, et al. Dissociation of FKBP 12.6 from ryanodine receptor type 2 is regulated by cyclic ADP-ribose but not ta-adrenergic stimulation in mouse cardiomyocytes. Cardiovasc Res, 2009, 84: 253–262
Zheng J, Wenzhi B, Miao L, et al. Ca(2+) release induced by cADP-ribose is mediated by FKBP12.6 proteins in mouse bladder smooth muscle. Cell Cal, 2010, 47: 449–457, 1:CAS:528:DC%2BC3cXmsVGrurk%3D
Ogunbayo O A, Zhu Y, Rossi D, et al. cADPR activates ryanodine receptors while NAADP activates two pore domain channels. J Biol Chem, 2011, 286: 9136–9140, 21216967, 1:CAS:528:DC%2BC3MXjtFOis7k%3D
Lee H C, Aarhus R, Graeff R, et al. Cyclic ADP ribose activation of the ryanodine receptor is mediated by calmodulin. Nature, 1994, 370: 307–309, 8035880, 1:CAS:528:DyaK2cXltVCrsr8%3D
Lee H C, Aarhus R, Graeff R M. Sensitization of calcium-induced calcium release by cyclic ADP-ribose and calmodulin. J Biol Chem, 1995, 270: 9060–9066, 7721819, 1:CAS:528:DyaK2MXlt1ajsLw%3D
Tanaka Y, Tashjian A H Jr. Calmodulin is a selective mediator of Ca2+-induced Ca2+ release via the ryanodine receptor-like Ca2+ channel triggered by cyclic ADP-ribose. Proc Natl Acad Sci USA, 1995, 92: 3244–3248, 7724546, 1:CAS:528:DyaK2MXltFSntL4%3D
Okabe E, Tsujimoto Y, Kobayashi Y. Calmodulin and cyclic ADP-ribose interaction in Ca2+ signaling related to cardiac sarcoplasmic reticulum: superoxide anion radical-triggered Ca2+ release. Antioxid Redox Signal, 2000, 2: 47–54, 11232599, 1:CAS:528:DC%2BD3cXisFWhur4%3D
Thomas J M, Summerhill R J, Fruen B R, et al. Calmodulin dissociation mediates desensitization of the cADPR-Induced Ca2+ release mechanism. Curr Biol, 2002, 12: 2018–2002, 12477390, 1:CAS:528:DC%2BD38XpsFehur8%3D
Wang Y X, Zheng Y M, Mei Q B, et al. FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. Am J Physiol, 2003, 286: C538–C546
Noguchi N, Takasawa S, Nata K, et al. Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsomes. J Biol Chem, 1997, 272: 3133–3136., 9013543, 1:CAS:528:DyaK2sXhtFenu70%3D
Morita K, Kitayama T, Kitayama S, et al. Cyclic ADP-ribose requires FK506-binding protein to regulate intracellular Ca2+ dynamics and catecholamine release in acetylcholine-stimulated bovine adrenal chromaffin cells. J Pharmacol Sci, 2006, 101: 40–51, 16648664, 1:CAS:528:DC%2BD28XlsVGns78%3D
Guse A H, Berg I, Dasilva C P, et al. Ca2+ entry induced by cyclic ADP-ribose in intact T-lymphocytes. J Biol Chem, 1997, 272: 8546–8550, 9079684, 1:CAS:528:DyaK2sXitF2mu7k%3D
Partida-Sanchez S, Cockayne D, Monard S, et al. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nature Med, 2001, 7: 1209–1216, 11689885, 1:CAS:528:DC%2BD3MXotlKlu7o%3D
Togashi K, Hara Y, Tominaga T, et al. TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J, 2006, 25: 1804–1815, 16601673, 1:CAS:528:DC%2BD28XktVGms7o%3D
Kolisek M, Beck A, Fleig A, et al. Cyclic ADP-ribose and hydrogen peroxide synergize with ADP-ribose in the activation of TRPM2 channels. Mol Cell, 2005, 18: 61–69, 15808509, 1:CAS:528:DC%2BD2MXjt1Oit7g%3D
Lange I, Penner R, Fleig A, et al. Synergistic regulation of endogenous TRPM2 channels by adenine dinucleotides in primary human neutrophils. Cell Cal, 2008, 44: 604–615, 1:CAS:528:DC%2BD1cXhtlGgs7nK
Eisfeld J, Luckhoff A. TRPM2. Handb Exp Pharmacol. 2007, 179: 237–252, 17217061, 1:CAS:528:DC%2BD2sXjtlGrtL8%3D
Gasser A, Glassmeier G, Fliegert R, et al. Activation of T cell calcium influx by the second messenger ADP-ribose. J Biol Chem, 2005, 281: 2489–2496, 16316998
Heiner I, Eisfeld J, Warnstedt M, et al. Endogenous ADP-ribose enables calcium-regulated cation currents through TRPM2 channels in neutrophil granulocytes. Biochem J, 2006, 9: 9
Starkus J, Beck A, Fleig A, et al. Regulation of TRPM2 by extra- and intracellular calcium. J Gen Physiol, 2007, 4: 427–440
Perraud A L, Fleig A, Dunn C A, et al. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature, 2001, 411: 595–599, 11385575, 1:CAS:528:DC%2BD3MXksVShsbo%3D
Togashi K, Inada H, Tominaga M. Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB). Br J Pharmacol, 2008, 153: 1324–1330, 18204483, 1:CAS:528:DC%2BD1cXjtleltb0%3D
Amina S, Hashii M, Ma W J, et al. Intracellular calcium elevation induced by extracellular application of cyclic-ADP-ribose or oxytocin is temperature-sensitive in rodent NG108-15 neuronal cells with or without exogenous expression of human oxytocin receptors. J Neuroendocrinol, 2010, 5: 460–466
Jin D, Liu H X, Hirai H, et al. CD38 is critical for social behaviour by regulating oxytocin secretion. Nature, 2007, 446: 41–45, 17287729, 1:CAS:528:DC%2BD2sXit1arsLw%3D
Scarfi S, Ferraris C, Fruscione F, et al. Cyclic ADP-ribose-mediated expansion and stimulation of human mesenchymal stem cells by the plant hormone abscisic acid. Stem Cells, 2008, 11: 2855–2864
Tao R, Sun H Y, Lau C P, et al. Cyclic ADP ribose is a novel regulator of intracellular Ca(2+) oscillations in human bone marrow mesenchymal stem cells. J Cell Mol Med, 2011, doi: 10.1111/j.1582-4934.2011.01263.x.
Aarhus R, Dickey D M, Graeff R M, et al. Activation and inactivation of Ca2+ release by NAADP+. J Biol Chem, 1996, 271: 8513–8516, 8621471, 1:CAS:528:DyaK28Xitlegurc%3D
Genazzani A A, Empson R M, Galione A. Unique inactivation properties of NAADP-sensitive Ca2+ release. J Biol Chem, 1996, 271: 11599–11602, 8662773, 1:CAS:528:DyaK28XjtV2lt78%3D
Lee H C, Aarhus R. Structural determinants of nicotinic acid adenine dinucleotide phosphate important for its calcium-mobilizing activity. J Biol Chem, 1997, 272: 20378–20383, 9252343, 1:CAS:528:DyaK2sXlsFKhu7o%3D
Lee H C. Modulator and messenger functions of cyclic ADP-ribose in calcium signaling. Re Prog Horm Res, 1996, 51: 355–88, 1:CAS:528:DyaK2sXktFKis74%3D
Lee H C, Aarhus R. Functional visualization of the separate but interacting calcium stores sensitive to NAADP and cyclic ADP-ribose. J Cell Sci, 2000, 113: 4413–4420, 11082034, 1:CAS:528:DC%2BD3MXmsVKmsw%3D%3D
Churchill G C, Okada Y, Thomas J M, et al. NAADP mobilizes Ca2+ from reserve granules, lysosome-related organelles, in sea urchin eggs. Cell, 2002, 111: 703–708, 12464181, 1:CAS:528:DC%2BD38XptlGrur4%3D
Kinnear N P, Boittin F X, Thomas J M, et al. Lysosome-Sarcoplasmic reticulum junctions: A trigger zone for calcium signalling by NAADP and endothelin-1. J Biol Chem, 2004, 279: 54319–54326, 15331591, 1:CAS:528:DC%2BD2cXhtVyltbvM
Galione A, Petersen O H. The NAADP Receptor: New receptors or new regulation? Mol Interv, 2005, 5: 73–79, 15821155, 1:CAS:528:DC%2BD2MXjvVyntLo%3D
Peiter E, Maathuis F J, Mills L N, et al. The vacuolar Ca2+-activated channel TPC1 regulates germination and stomatal movement. Nature, 2005, 434: 404–408, 15772667, 1:CAS:528:DC%2BD2MXit1yru7k%3D
Calcraft P J, Ruas M, Pan Z, et al. NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature, 2009, 459: 596–601, 19387438, 1:CAS:528:DC%2BD1MXkvVKns78%3D
Brailoiu E, Churamani D, Cai X, et al. Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. J Cell Biol, 2009, 186: 201–209, 19620632, 1:CAS:528:DC%2BD1MXpsVGisL8%3D
Zong X, Schieder M, Cuny H, et al. The two-pore channel TPCN2 mediates NAADP-dependent Ca2+-release from lysosomal stores. Pflugers Arch, 2009, 458: 891–899, 19557428, 1:CAS:528:DC%2BD1MXptlamsL8%3D
Schieder M, Roetzer K, Brueggemann A, et al. Characterization of two pore channel 2 (TPCN2) -mediated Ca2+ currents in isolated lysosomes. J Biol Chem, 2010, 285: 21219–21222, 20495006, 1:CAS:528:DC%2BC3cXos1WrsL0%3D
Ruas M, Rietdorf K, Arredouani A, et al. Purified TPC isoforms form NAADP receptors with distinct roles for Ca2+ signaling and endolysosomal trafficking. Curr Biol, 2010, Mar 24. [Epub ahead of print]
Pitt S J, Funnell T, Sitsapesan M, et al. TPC2 is a novel NAADP-sensitive ca2+-release channel, operating as a dual sensor of luminal pH and Ca2+. J Biol Chem, 2010, 285: 35039–35046, 20720007, 1:CAS:528:DC%2BC3cXhtlGktbnP
Galione A, Evans A M, Ma J, et al. The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca2+ release channels. Pflugers Arch, 2009, 458: 869–876, 19475418, 1:CAS:528:DC%2BD1MXptlamsb8%3D
Rusinko N, Lee H C. Widespread occurrence in animal tissues of an enzyme catalyzing the conversion of NAD+ into a cyclic metabolite with intracellular Ca2+-mobilizing activity. J Biol Chem, 1989, 264: 11725–11731, 2745413, 1:CAS:528:DyaL1MXlslWnurk%3D
Hellmich M R, Strumwasser F. Purification and characterization of a molluscan egg-specific NADase, a second-messenger enzyme. Cell Regul, 1991, 2: 193–202, 1650254, 1:CAS:528:DyaK3MXit1Cht7w%3D
Lee H C, Aarhus R. ADP-ribosyl cyclase: an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite. Cell Regul, 1991, 2: 203–209, 1830494, 1:CAS:528:DyaK3MXltV2jtro%3D
Graeff R M, Walseth T F, Fryxell K, et al. Enzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activity. J Biol Chem, 1994, 269: 30260–30267, 7982936, 1:CAS:528:DyaK2MXhs12ntrk%3D
States D J, Walseth T F, Lee H C. Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and human lymphocyte antigen CD38. Trends Biochem Sci, 1992, 17: 495, 1471258, 1:CAS:528:DyaK3sXhvVGisw%3D%3D
Howard M, Grimaldi J C, Bazan J F, et al. Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science, 1993, 262: 1056–1059, 8235624, 1:CAS:528:DyaK2cXmsVWn
Lee H C, Zocchi E, Guida L, et al. Production and hydrolysis of cyclic ADP-ribose at the outer surface of human erythrocytes. Biochem Biophys Res Commun, 1993, 191: 639–645, 8461019, 1:CAS:528:DyaK3sXktVGltLg%3D
Takasawa S, Tohgo A, Noguchi N, et al. Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP. J Biol Chem, 1993, 268: 26052–26054, 8253715, 1:CAS:528:DyaK3sXmsVKntbc%3D
Kim H, Jacobson E L, Jacobson M K. Synthesis and degradation of cyclic ADP-ribose by NAD glycohydrolases. Science, 1993, 261: 1330–1333, 8395705, 1:CAS:528:DyaK3sXmsVCjtbw%3D
Graeff R M, Mehta K, Lee H C. GDP-ribosyl cyclase activity as a measure of CD38 induction by retinoic acid in HL-60 cells. Biochem. Biophys Res Commun, 1994, 205: 722–727, 7999103, 1:CAS:528:DyaK2MXis1altb0%3D
Graeff R M, Walseth T F, Hill H K, et al. Fluorescent analogs of cyclic ADP-ribose: synthesis, spectral characterization, and use. Biochemistry, 1996, 35: 379–386, 8555207, 1:CAS:528:DyaK2MXhtVSmtrjK
Graeff R, Lee H C. A novel cycling assay for cellular cyclic ADP-ribose with nanomolar sensitivity. Biochem J, 2002, 361: 379–384, 11772410, 1:CAS:528:DC%2BD38XitVGqsL0%3D
Kato I, Yamamoto Y, Fujimura M, et al. CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i and insulin secretion. J Biol Chem, 1999, 274: 1869–1872, 9890936, 1:CAS:528:DyaK1MXovVGisg%3D%3D
Fukushi Y, Kato I, Takasawa S, et al. Identification of cyclic ADP-ribose-dependent mechanisms in pancreatic muscarinic Ca2+ signaling using CD38 knockout mice. J Biol Chem, 2001, 276: 649–655, 11001947, 1:CAS:528:DC%2BD3MXmtFWisg%3D%3D
Partida-Sanchez S, Goodrich S, Kusser K, et al. Regulation of dendritic cell trafficking by the ADP-ribosyl cyclase CD38; Impact on the development of humoral immunity. Immunity, 2004, 20: 279–291, 15030772, 1:CAS:528:DC%2BD2cXis1KhtrY%3D
Sun L, Iqbal J, Dolgilevich S, et al. Disordered osteoclast formation and function in a CD38 (ADP-ribosyl cyclase)-deficient mouse establishes an essential role for CD38 in bone resorption. FASEB J, 2003, 17: 369–375, 12631576, 1:CAS:528:DC%2BD3sXitFeitbc%3D
Deshpande D A, White T A, Guedes A G P, et al. Altered airway responsiveness in CD38 deficient mice. Am J Respir Cell Mol Biol, 2005, 32: 149–156, 15557017, 1:CAS:528:DC%2BD2MXhtFCnsrs%3D
Mitsui-Saito M, Kato I, Takasawa S, et al. CD38 gene disruption inhibits the contraction induced by alpha-adrenoceptor stimulation in mouse aorta. J Vet Med Sci, 2003, 65: 1325–1330, 14709821, 1:CAS:528:DC%2BD2cXmsVKhug%3D%3D
Takahashi J, Kagaya Y, Kato I, et al. Deficit of CD38/cyclic ADP-ribose is differentially compensated in hearts by gender. Biochem Biophys Res Commun, 2003, 312: 434–440, 14637156, 1:CAS:528:DC%2BD3sXptVelur4%3D
Malavasi F, Deaglio S, Funaro A, et al. Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev, 2008, 88: 841–886, 18626062, 1:CAS:528:DC%2BD1cXpslKgs7s%3D
Billington R A, Ho A, Genazzani A A. Nicotinic acid adenine dinucleotide phosphate (NAADP) is present at micromolar concentrations in sea urchin spermatozoa. J Physiol, 2002, 544.1: 107–112
Churchill G C, O’Neill J S, Masgrau R, et al. Sperm deliver a new second messenger: NAADP. Curr Biol, 2003, 13: 125–128, 12546785, 1:CAS:528:DC%2BD3sXmsFerug%3D%3D
Churamani D, Carrey E A, Dickinson G D, et al. Determination of cellular nicotinic acid adenine dinucleotide phosphate (NAADP) levels. Biochem J, 2004, 380: 449–454, 14984366, 1:CAS:528:DC%2BD2cXksFyiu7Y%3D
Aarhus R, Graeff R M, Dickey D M, et al. ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP. J Biol Chem, 1995, 270: 30327–30333, 8530456, 1:CAS:528:DyaK28XhtFKiug%3D%3D
Kim S Y, Cho B H, Kim U H. CD38-mediated Ca2+ signaling contributes to angiotensin II-induced activation of hepatic stellate cells: attenuation of hepatic fibrosis by CD38 ablation. J Biol Chem, 2010, 285: 576–582, 19910464, 1:CAS:528:DC%2BD1MXhs1SqtrzI
Rah S Y, Mushtaq M, Nam T S, et al. Generation of cyclic ADP-Ribose and nicotinic acid adenine dinucleotide phosphate by CD38 for Ca2+ signaling in interleukin-8-treated lymphokine-activated killer cells. J Biol Chem, 2010, 285: 21877–21887, 20442403, 1:CAS:528:DC%2BC3cXos1Wrurc%3D
Cosker F, Cheviron N, Yamasaki M, et al. The ecto-enzyme CD38 is a NAADP synthase which couples receptor activation to Ca2+ mobilization from lysosomes in pancreatic acinar cells. J Biol Chem, 2010, 285: 38251–38259, 20870729, 1:CAS:528:DC%2BC3cXhsVOku7zF
Jackson D G, Bell J I. Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous patern of expression during lymphocyte differentiation. J Immunol, 1990, 144: 2811–2815, 2319135, 1:CAS:528:DyaK3cXltFSiurc%3D
Prasad G S, McRee D E, Stura E A, et al. Crystal structure of Aplysia ADP ribosyl cyclase, a homologue of the bifunctional ectozyme CD38. Nature Struct Biol, 1996, 3: 957–964, 8901875, 1:CAS:528:DC%2BD38Xms1Cltrc%3D
Munshi C, Baumann C, Levitt D, et al. The homo-dimeric form of ADP-ribosyl cyclase in solution. Biochim Biophys Acta, 1998, 1388: 428–436, 9858777, 1:CAS:528:DyaK1cXnslOktbs%3D
Munshi C, Thiel D J, Mathews I I, et al. Characterization of the active site of ADP-ribosyl cyclase. J Biol Chem, 1999, 274: 30770–30777, 10521467, 1:CAS:528:DyaK1MXntVSmtLk%3D
Liu Q, Kriksunov I A, Graeff R, et al. Crystal structure of human CD38 extracellular domain. Structure, 2005, 13: 1331–1339, 16154090, 1:CAS:528:DC%2BD2MXpvFentrk%3D
Liu Q, Kriksunov I A, Graeff R, et al. Structural basis for formation and hydrolysis of calcium messenger cyclic ADP-ribose by human CD38. J Biol Chem, 2007, 282: 5853–5861, 17182614, 1:CAS:528:DC%2BD2sXhvVaiu7c%3D
Liu Q, Graeff R, Kriksunov I A, et al. Conformational closure of the catalytic site of human CD38 induced by calcium. Biochemistry, 2008, 47: 13966–13973, 1:CAS:528:DC%2BD1cXhsVOjsLrO
Munshi C, Aarhus R, Graeff R, et al. Identification of the enzymatic active site of CD38 by site-directed mutagenesis. J Biol Chem, 2000, 275: 21566–21571, 10781610, 1:CAS:528:DC%2BD3cXkvFGisb8%3D
Graeff R, Liu Q, Kriksunov I A, et al. Mechanism of cyclizing NAD to cyclic ADP-ribose by ADP-ribosyl cyclase and CD38. J Biol Chem, 2009, 284: 27629–27636, 19640843, 1:CAS:528:DC%2BD1MXhtFyjs7zI
Graeff R, Munshi C, Aarhus R, et al. A single residue at the active site of CD38 determines its NAD cyclizing and hydrolyzing activities. J Biol Chem, 2001, 276: 12169–12173, 11278881, 1:CAS:528:DC%2BD3MXjtFyltLY%3D
Graeff R, Liu Q, Kriksunov I A, et al. Acidic residues at the active sites of CD38 and ADP-ribosyl cyclase determine NAADP synthesis and hydrolysis activities. J Biol Chem, 2006, 281: 28951–28957, 16861223, 1:CAS:528:DC%2BD28XpvFanu7o%3D
Liu Q, Kriksunov I A, Graeff R, et al. Structural basis for the mechanistic understanding of human CD38 controlled multiple catalysis. J Biol Chem, 2006, 281: 32861–32869, 16951430, 1:CAS:528:DC%2BD28XhtFSrtrrJ
Liu Q, Kriksunov I A, Jiang H, et al. Covalent and noncovalent intermediates of an NAD utilizing enzyme, human CD38. Chem Biol, 2008, 15: 1068–1078, 18940667, 1:CAS:528:DC%2BD1cXht1KmsrfF
Zhang H, Graeff R, Chen Z, et al. Dynamic conformations of the CD38-mediated NAD cyclization captured in a single crystal. J Mol Biol, 2011, 405: 1070–1078, 21134381, 1:CAS:528:DC%2BC3MXjvFKltQ%3D%3D
Mohanty B, Serrano P, Pedrini B, et al. Comparison of NMR and crystal structures for the proteins TM1112 and TM1367. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2010, 66: 1381–1392, 20944235
Galione A, White A, Willmott N, et al. cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature, 1993, 365: 456–459, 7692303, 1:CAS:528:DyaK3sXmt1aht78%3D
Willmott N, Sethi J K, Walseth T F, et al. Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway. J Biol Chem, 1996, 271: 3699–705, 8631983, 1:CAS:528:DyaK28XhtFOktLY%3D
Wilson H L, Galione A. Differential regulation of nicotinic acid adenine dinucleotide phosphate and cADP-ribose production by cAMP and cGMP. Biochem J, 1998, 331: 837–843, 9560312, 1:CAS:528:DyaK1cXjt12hsrc%3D
Graeff R M, Franco L, De Flora A, et al. Cyclic GMP-dependent and -independent effects on the synthesis of the calcium messengers cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate. J Biol Chem, 1998, 273: 118–125, 9417055, 1:CAS:528:DyaK1cXjvFShsg%3D%3D
Reyes-Harde M, Empson R, Potter B V L, et al. Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus. Proc Natl Acad Sci USA, 1999, 96: 4061–4066, 10097163, 1:CAS:528:DyaK1MXjslCht7w%3D
Shawl A I, Park K H, Kim U H. Insulin receptor signaling for the proliferation of pancreatic beta-cells: Involvement of Ca2+ second messengers, IP3, NAADP and cADPR. Islets, 2009, 1: 216–223, 21099275
Sternfeld L, Krause E, Guse A H, et al. Hormonal control of ADP-ribosyl cyclase in pancreatic acinar cells from rat. J Biol Chem, 2003, 36: 33629–33636
Xie G H, Rah S Y, Kim S J, et al. ADP-ribosyl cyclase couples to cyclic AMP signaling in the cardiomyocytes. Biochem Biophys Res Commun, 2005, 330: 1290–1298, 15823583, 1:CAS:528:DC%2BD2MXjtVyksLs%3D
Bruzzone S, Moreschi I, Usai C, et al. Abscisic acid is an endogenous cytokine in human granulocytes with cyclic ADP-ribose as second messenger. Proc Natl Acad Sci USA, 2007, 104: 5759–5764, 17389374, 1:CAS:528:DC%2BD2sXkt1Kgsbs%3D
Magnone M, Bruzzone S, Guida L, et al. Abscisic acid released by human monocytes activates monocytes and vascular smooth muscle cell responses involved in atherogenesis. J Biol Chem, 2009, 284: 17808–17818, 19332545, 1:CAS:528:DC%2BD1MXnsVWksbo%3D
Bruzzone S, Moreschi I, Guida L, et al. Extracellular NAD+ regulates intracellular calcium levels and induces activation of human granulocytes. Biochem J, 2006, 393: 697–704, 16225456, 1:CAS:528:DC%2BD28XmtlOltg%3D%3D
De Flora A, Guida L, Franco L, et al. The CD38/Cyclic ADP-ribose system-A topological paradox. Int J Biochem Cell Biol, 1997, 29: 1149–1166, 9438379
De Flora A, Zocchi E, Guida L, et al. Autocrine and paracrine calcium signaling by the CD38/NAD+/cyclic ADP-ribose system. Ann NY Acad Sci, 2004, 1028: 176–191, 15650244
Bruzzone S, Franco L, Guida L, et al. A self-restricted CD38-connexin 43 cross-talk affects NAD+ and cyclic ADP-ribose metabolism and regulates intracellular calcium in 3T3 fibroblasts. J Biol Chem, 2001, 276: 48300–48308, 11602597, 1:CAS:528:DC%2BD38XltVGr
Bruzzone S, Guida L, Zocchi E, et al. Connexin 43 hemi channels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells. Faseb J, 2001, 15: 10–12, 11099492, 1:CAS:528:DC%2BD3MXht1Snsrc%3D
Guida L, Bruzzone S, Sturla L, et al. Equilibrative and concentrative nucleoside transporters mediate influx of extracellular cyclic ADP-Ribose into 3T3 murine fibroblasts. J Biol Chem, 2002, 277: 47097–47105, 12368285, 1:CAS:528:DC%2BD38XptFSktLs%3D
Guida L, Franco L, Bruzzone S, et al. Concentrative influx of functionally active cyclic ADP-ribose in dimethylsulfoxide-differen tiated HL-60 cells. J Biol Chem, 2004, 279: 22066–22075, 15028729, 1:CAS:528:DC%2BD2cXjvF2rs78%3D
Yamada M, Mizuguchi M, Otsuka N, et al. Ultrastructural localization of CD38 immunoreactivity in rat brain. Brain Res, 1997, 756: 52–60, 9187313, 1:CAS:528:DyaK2sXislehurc%3D
Kou W, Banerjee S, Eudy J, et al. CD38 regulation in activated astrocytes: Implications for neuroinflammation and HIV-1 brain infection. J Neurosci Res, 2009, 87: 2326–2339, 19365854, 1:CAS:528:DC%2BD1MXnt1Sit7o%3D
Davis L C, Morgan A J, Ruas M, et al. Ca2+ Signaling occurs via second messenger release from intraorganelle synthesis sites. Curr Biol, 2008, 18: 1612–1618, 18951023, 1:CAS:528:DC%2BD1cXhtlSgsbfP
Adebanjo O A, Anandatheerthavarada H K, Koval A P, et al. A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis. Nature Cell Biol, 1999, 1: 409–414, 10559984, 1:CAS:528:DyaK1MXns1Gqsb8%3D
Khoo K M, Han M-K, Park J B, et al. Localization of the cyclic ADP-ribose-dependent calcium signaling pathway in hepatocyte nucleus. J Biol Chem, 2000, 275: 24807–24817, 10818108, 1:CAS:528:DC%2BD3cXlsl2jt78%3D
Yalcintepe L, Albeniz I, Adin-Cinar S, et al. Nuclear CD38 in retinoic acid-induced HL-60 cells. Exper Cell Res, 2005, 303: 14–21, 1:CAS:528:DC%2BD2cXhtVaqtrfJ
Higy M, Junne T, Spiess M. Topogenesis of membrane proteins at the endoplasmic reticulum. Biochemistry, 2004, 43: 12716–12722, 15461443, 1:CAS:528:DC%2BD2cXnsFOgtrY%3D
Seppala S, Slusky J S, Lloris-Garcera P, et al. Control of membrane protein topology by a single C-terminal residue. Science, 2010, 328: 1698–1700, 20508091
Hegde R S, Mastrianni J A, Scott M R, et al. A transmembrane form of the prion protein in neurodegenerative disease. Science, 1998, 279: 827–834, 9452375, 1:CAS:528:DyaK1cXhtVKrtLk%3D
Hegde R S, Voigt S, Lingappa V R. Regulation of Protein topology by trans-acting factors at the endoplasmic reticulum. Mol Cell, 1998, 2: 85–91, 9702194, 1:CAS:528:DyaK1cXltVektbs%3D
Stewart R S, Harris D A. A transmembrane form of the prion protein is localized in the Golgi apparatus of neurons. J Biol Chem, 2005, 280: 15855–15864, 15671025, 1:CAS:528:DC%2BD2MXjtleisLc%3D
Stewart R S, Harris D A. Mutational analysis of topological determinants in prion protein (PrP) and measurement of transmembrane and cytosolic PrP during prion infection. J Biol Chem, 2003, 278: 45960–45968, 12933795, 1:CAS:528:DC%2BD3sXosl2itLg%3D
Cumming R C, Andon N L, Haynes P A, et al. Protein disulfide bond formation in the cytoplasm during oxidative stress. J Biol Chem, 2004, 279: 21749–21758, 15031298, 1:CAS:528:DC%2BD2cXjvF2ktb0%3D
Brennan J P, Wait R, Begum S, et al. Detection and mapping of widespread intermolecular protein disulfide formation during cardiac oxidative stress using proteomics with diagonal electrophoresis. J Biol Chem, 2004, 279: 41352–41360, 15292244, 1:CAS:528:DC%2BD2cXnvFWhtrk%3D
Stewart E J, Åslund F, Beckwith J. Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role reversal for the thioredoxins. EMBO J, 1998, 17: 5543–5550, 9755155, 1:CAS:528:DyaK1cXmvVyjsrY%3D
Zhao Y J, Zhang H M, Lam C M C, et al. Cytosolic CD38 forms intact disulfides and is active in elevating intracellular cyclic ADP-ribose. J Biol Chem, 2011, 286: 22170–22177, 21524995, 1:CAS:528:DC%2BC3MXns1Kks70%3D
Harden A, Young W J. The alcoholic ferment of yeast-juice. Proc R Soc London, 1906, 78: 369–375
Warburg O, Christian W. Pyridin, the hydrogen-transferring component of the fermentation enzymes (pyridine nucleotide). Biochem Z, 1936, 287: 291, 1:CAS:528:DyaA2sXlsVWi
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Lee, H.C. Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. Sci. China Life Sci. 54, 699–711 (2011). https://doi.org/10.1007/s11427-011-4197-3
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DOI: https://doi.org/10.1007/s11427-011-4197-3