title: The calcium-mobilizing messenger nicotinic acid adenine dinucleotide phosphate participates in sperm activation by mediating the acrosome reaction.
abstract: Before a sperm can fertilize an egg it must undergo a final activation step induced by the egg termed the acrosome reaction. During the acrosome reaction a lysosome-related organelle, the acrosome, fuses with the plasma membrane to release hydrolytic enzymes and expose an egg-binding protein. Because NAADP (nicotinic acid adenine dinucleotide phosphate) releases Ca(2+) from acidic lysosome-related organelles in other cell types, we investigated a possible role for NAADP in mediating the acrosome reaction. We report that NAADP binds with high affinity to permeabilized sea urchin sperm. Moreover, we used Mn(2+) quenching of luminal fura-2 and (45)Ca(2+) to directly demonstrate NAADP regulation of a cation channel on the acrosome. Additionally, we show that NAADP synthesis occurs through base exchange and is driven by an increase in Ca(2+). We propose a new model for acrosome reaction signaling in which Ca(2+) influx initiated by egg jelly stimulates NAADP synthesis and that this NAADP acts on its receptor/channel on the acrosome to release Ca(2+) to drive acrosomal exocytosis.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom.
authors.forename: Sridhar R
authors.initials: SR
authors.lastname: Vasudevan
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Lewis
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Chan
authors.forename: Claire L
authors.initials: CL
authors.lastname: Machin
authors.forename: Debroshi
authors.initials: D
authors.lastname: Sinha
authors.forename: Antony
authors.initials: A
authors.lastname: Galione
authors.forename: Grant C
authors.initials: GC
authors.lastname: Churchill
mesh_terms: D000177:Acrosome / Q000378:metabolism; D020101:Acrosome Reaction; D000818:Animals; D002118:Calcium / Q000737:chemistry; D002412:Cations; D005089:Exocytosis; D005260:Female; D016257:Fura-2 / Q000737:chemistry; D008297:Male; D008345:Manganese / Q000737:chemistry; D009249:NADP / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D012617:Sea Urchins; D015398:Signal Transduction; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D002412:Cations; D008345:Manganese; D009249:NADP; C024376:NAADP; D002118:Calcium; D016257:Fura-2
references.citation: Biochem J. 2009 Apr 1;419(1):91-7, 2 p following 97
references.pmid: 19090786
references.citation: J Biol Chem. 1987 Jul 15;262(20):9561-8
references.pmid: 3496336
references.citation: Biochem J. 2008 Apr 1;411(1):63-70
references.pmid: 18215126
references.citation: Biochem Biophys Res Commun. 2006 Sep 22;348(2):329-36
references.pmid: 16890912
references.citation: Biochem J. 1984 May 1;219(3):965-70
references.pmid: 6743255
references.citation: Mol Interv. 2005 Apr;5(2):73-9
references.pmid: 15821155
references.citation: J Biol Chem. 2003 Mar 28;278(13):11057-64
references.pmid: 12538591
references.citation: Cell Calcium. 2004 Dec;36(6):515-24
references.pmid: 15488601
references.citation: Cell Regul. 1991 Mar;2(3):203-9
references.pmid: 1830494
references.citation: Physiol Rev. 1999 Apr;79(2):481-510
references.pmid: 10221988
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466-70
references.pmid: 2138778
references.citation: Biochem Biophys Res Commun. 2006 Jan 6;339(1):443-9
references.pmid: 16297861
references.citation: Biochemistry. 1998 Sep 22;37(38):13239-49
references.pmid: 9748331
references.citation: J Biol Chem. 2000 Dec 8;275(49):38687-92
references.pmid: 11006280
references.citation: Biochem J. 1997 Oct 15;327 ( Pt 2):545-52
references.pmid: 9359428
references.citation: Biochem Biophys Res Commun. 2000 Sep 16;276(1):112-6
references.pmid: 11006092
references.citation: Dev Biol. 2001 Aug 1;236(1):220-9
references.pmid: 11456456
references.citation: Cell. 2002 Nov 27;111(5):703-8
references.pmid: 12464181
references.citation: Br J Pharmacol. 1997 Aug;121(7):1489-95
references.pmid: 9257932
references.citation: J Biol Chem. 1988 Jan 15;263(2):690-5
references.pmid: 2447081
references.citation: PLoS One. 2007 Aug 29;2(8):e797
references.pmid: 17726527
references.citation: J Biol Chem. 1988 Oct 25;263(30):15297-303
references.pmid: 2459122
references.citation: Structure. 2004 Mar;12(3):477-86
references.pmid: 15016363
references.citation: J Cell Sci. 2000 Dec;113 Pt 24:4413-20
references.pmid: 11082034
references.citation: J Biol Chem. 2001 Apr 6;276(14):11223-5
references.pmid: 11139579
references.citation: Curr Biol. 2003 Jan 21;13(2):125-8
references.pmid: 12546785
references.citation: J Biol Chem. 1995 Feb 3;270(5):2152-7
references.pmid: 7836444
references.citation: Zygote. 1997 Nov;5(4):355-64
references.pmid: 9563683
references.citation: Biochem Biophys Res Commun. 2003 May 2;304(2):285-92
references.pmid: 12711312
references.citation: J Biol Chem. 2000 Mar 24;275(12):8301-6
references.pmid: 10722659
references.citation: Biochem J. 1996 Oct 15;319 ( Pt 2):613-7
references.pmid: 8912702
references.citation: J Biol Chem. 1996 Apr 12;271(15):8513-6
references.pmid: 8621471
references.citation: J Biol Chem. 1985 Mar 25;260(6):3440-50
references.pmid: 3838314
references.citation: Nature. 1999 Mar 4;398(6722):74-6
references.pmid: 10078532
references.citation: Anal Biochem. 2007 Dec 1;371(1):26-36
references.pmid: 17919448
references.citation: Dev Biol. 2006 Jun 1;294(1):24-38
references.pmid: 16545362
references.citation: Biochem J. 2002 Jan 15;361(Pt 2):379-84
references.pmid: 11772410
references.citation: J Biol Chem. 2004 Feb 20;279(8):7234-40
references.pmid: 14660554
references.citation: FEBS Lett. 1985 Jul 8;186(2):175-9
references.pmid: 2408921
references.citation: Dev Biol. 1978 Aug;65(2):483-95
references.pmid: 680373
references.citation: Science. 2001 May 4;292(5518):920-3
references.pmid: 11340203
references.citation: Cell Signal. 2008 Dec;20(12):2347-55
references.pmid: 18824228
references.citation: J Physiol. 2002 Oct 1;544(Pt 1):107-12
references.pmid: 12356884
references.citation: J Biol Chem. 1999 Oct 22;274(43):30770-7
references.pmid: 10521467
references.citation: Biochem Biophys Res Commun. 2004 Jan 23;313(4):894-901
references.pmid: 14706626
references.citation: Biochem J. 2007 Mar 1;402(2):301-10
references.pmid: 17117921
references.citation: Biochem J. 2004 Jul 1;381(Pt 1):147-54
references.pmid: 15084143
references.citation: Nature. 1994 Aug 11;370(6489):474-7
references.pmid: 8047168
references.citation: J Biol Chem. 2007 Dec 28;282(52):37730-7
references.pmid: 17959608
references.citation: Nat Rev Mol Cell Biol. 2005 Jun;6(6):499-505
references.pmid: 15928713
references.citation: Curr Biol. 2008 Oct 28;18(20):1612-8
references.pmid: 18951023
references.citation: Parasitol Today. 1999 Nov;15(11):443-8
references.pmid: 10511686
references.citation: J Biol Chem. 1996 May 17;271(20):11599-602
references.pmid: 8662773
references.citation: FASEB J. 2000 Jul;14(10):1265-78
references.pmid: 10877819
references.citation: Cell Calcium. 2006 Aug;40(2):241-52
references.pmid: 16797697
references.citation: Reproduction. 2006 Jun;131(6):977-88
references.pmid: 16735537
references.citation: Biochem J. 2004 Jun 1;380(Pt 2):449-54
references.pmid: 14984366
references.citation: Dev Biol. 1997 Dec 1;192(1):125-35
references.pmid: 9405102
references.citation: J Biol Chem. 2005 Oct 7;280(40):33693-6
references.pmid: 16076847
references.citation: J Biol Chem. 2002 Dec 20;277(51):49326-31
references.pmid: 12379648
references.citation: J Cell Physiol. 2005 Mar;202(3):663-71
references.pmid: 15389568
references.citation: Sci STKE. 2000 Jul 11;2000(40):pe1
references.pmid: 11752596
references.citation: J Biol Chem. 1995 Dec 22;270(51):30327-33
references.pmid: 8530456
references.citation: Biochem J. 2000 Dec 15;352 Pt 3:725-9
references.pmid: 11104679
references.citation: Proc Natl Acad Sci U S A. 1977 Jun;74(6):2456-60
references.pmid: 267939