A single residue in a novel ADP-ribosyl cyclase controls production of the calcium-mobilizing messengers cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate.
Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate are ubiquitous calcium-mobilizing messengers produced by the same family of multifunctional enzymes, the ADP-ribosyl cyclases. Not all ADP-ribosyl cyclases have been identified, and how production of different messengers is achieved is incompletely understood. Here, we report the cloning and characterization of a novel ADP-ribosyl cyclase (SpARC4) from the sea urchin, a key model organism for the study of calcium-signaling pathways. Like several other members of the ADP-ribosyl cyclase superfamily, SpARC4 is a glycoprotein targeted to the plasma membrane via a glycosylphosphatidylinositol anchor. However, unlike most other members, SpARC4 shows a remarkable preference for producing cyclic ADP-ribose over nicotinic acid adenine dinucleotide phosphate. Mutation of a single residue (tyrosine 142) within a noncanonical active site reversed this striking preference. Our data highlight further diversification of this unusual enzyme family, provide mechanistic insight into multifunctionality, and suggest that different ADP-ribosyl cyclases are fine-tuned to produce specific calcium-mobilizing messengers.
Ramakrishnan
Latha
L
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
Muller-Steffner
Hélène
H
Bosc
Christophe
C
Vacquier
Victor D
VD
Schuber
Francis
F
Moutin
Marie-Jo
MJ
Dale
Leslie
L
Patel
Sandip
S
D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008845:Microinjections; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D047270:Strongylocentrotus purpuratus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology
D036563:Cyclic ADP-Ribose; D014443:Tyrosine; D009249:NADP; C024376:NAADP; D036541:ADP-ribosyl Cyclase
J Biol Chem. 1995 Feb 3;270(5):2152-7
7836444
Annu Rev Pharmacol Toxicol. 2001;41:317-45
11264460
J Biol Chem. 1987 Jul 15;262(20):9561-8
3496336
J Biol Chem. 2006 Oct 27;281(43):32861-9
16951430
J Biol Chem. 2003 Sep 5;278(36):33629-36
12807891
Fertil Steril. 2006 Oct;86(4):891-8
16904113
Biochem J. 2003 Oct 15;375(Pt 2):395-403
12852785
Biochem Biophys Res Commun. 2005 May 20;330(4):1290-8
15823583
Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H274-82
16473958
J Biol Chem. 1995 Dec 22;270(51):30327-33
8530456
Sci Signal. 2009 May 19;2(71):ra23
19454650
Cell Regul. 1991 Mar;2(3):203-9
1830494
J Biol Chem. 2001 Apr 13;276(15):12169-73
11278881
Dev Dyn. 2005 Jul;233(3):1038-44
15844195
J Biol Chem. 1999 Jan 22;274(4):1869-72
9890936
J Biol Chem. 1994 Nov 18;269(46):28555-7
7961800
J Biol Chem. 2001 Jan 5;276(1):649-55
11001947
J Biol Chem. 1998 Jan 2;273(1):118-25
9417055
Nature. 2007 Mar 1;446(7131):41-5
17287729
Mol Cell Biochem. 1999 Mar;193(1-2):89-98
10331643
Biochemistry. 2005 Aug 23;44(33):11082-97
16101292
Curr Biol. 2009 Jul 14;19(13):R521-3
19602416
Cell. 2002 Nov 27;111(5):703-8
12464181
FEBS Lett. 1996 Nov 4;396(2-3):327-32
8915013
PLoS One. 2007 Aug 29;2(8):e797
17726527
Nature. 2009 May 28;459(7246):596-600
19387438
J Biol Chem. 2003 Oct 17;278(42):40670-8
12909645
Curr Mol Med. 2004 May;4(3):249-61
15101683
Biochem Biophys Res Commun. 1998 Dec 18;253(2):246-52
9878523
J Biol Chem. 2002 Nov 15;277(46):43717-23
12223470
Sci Signal. 2009 Nov 03;2(95):pe69
19887679
Science. 1993 Nov 12;262(5136):1056-9
8235624
Biochem J. 2000 Jul 1;349(Pt 1):203-10
10861229
Cell Regul. 1991 Mar;2(3):211-8
1650255
Nature. 2001 May 31;411(6837):595-9
11385575
J Biol Chem. 1994 Dec 2;269(48):30260-7
7982936
J Biol Chem. 2009 Oct 2;284(40):27629-36
19640843
Biochem J. 2002 Oct 15;367(Pt 2):423-31
12102654
Biochem J. 2008 Apr 1;411(1):63-70
18215126
J Cell Biol. 2009 Jul 27;186(2):201-9
19620632
Sci Signal. 2008 Nov 04;1(44):re10
18984909
Nature. 1999 Mar 4;398(6722):70-3
10078531
J Biol Chem. 2008 Oct 10;283(41):27859-27870
18632662
Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21
11413485
Biochemistry. 2007 Apr 3;46(13):4100-9
17341094
J Biol Chem. 2000 Jul 14;275(28):21566-71
10781610
Nat Struct Biol. 1996 Nov;3(11):957-64
8901875
Trends Cell Biol. 2010 May;20(5):277-86
20303271
J Biol Chem. 2003 May 16;278(20):18478-84
12637569
J Biol Chem. 2010 Jan 29;285(5):2897-901
19940116
Cell Signal. 2008 Dec;20(12):2347-55
18824228
Development. 2005 Feb;132(3):591-602
15634697
Biochem Biophys Res Commun. 1997 May 8;234(1):252-6
9168998
J Biol Chem. 1999 Oct 22;274(43):30770-7
10521467
J Mol Biol. 2002 Feb 22;316(3):711-23
11866528
Nat Med. 2001 Nov;7(11):1209-16
11689885
Cell Regul. 1991 Mar;2(3):193-202
1650254
Curr Biol. 2008 Oct 28;18(20):1612-8
18951023
Science. 1991 Sep 6;253(5024):1143-6
1909457
J Biol Chem. 2010 Jan 1;285(1):576-82
19910464
FEBS Lett. 1994 Dec 19;356(2-3):244-8
7805847
J Biol Chem. 2001 Apr 6;276(14):11180-8
11116136
Am J Physiol Cell Physiol. 2007 Jan;292(1):C227-39
16790499
Ann N Y Acad Sci. 2004 Dec;1028:176-91
15650244
Biochemistry. 2006 Oct 3;45(39):11867-78
17002287