title: VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes.
abstract: ANP is a peptide released by cardiac myocytes that regulates blood pressure and natriuresis. However, the molecular mechanisms controlling ANP release from cardiac myocytes are not defined. We now identify three components of the exocytic machinery that regulate ANP release from atrial myocytes. We found that cardiac myocytes express N-ethylmaleimide sensitive factor (NSF), soluble NSF attachment protein (α-SNAP), and SNAP receptors (SNAREs). Additionally we found that specific SNARE molecules, VAMP-1 and VAMP-2, both co-sediment and co-localize with ANP. Also, one SNARE molecule, syntaxin-4, partially co-sediments and partially co-localizes with ANP. Furthermore, these three SNAREs, syntaxin-4 and VAMP-1 and VAMP-2, form a SNARE complex inside cardiac myocytes. Finally, knockdown of VAMP-1, VAMP-2, or syntaxin-4 blocks regulated release of ANP. In contrast, silencing of VAMP-3 did not have an effect on ANP release. Our data suggest that three specific SNAREs regulate cardiac myocyte exocytosis of ANP. Pathways that modify the exocytic machinery may influence natriuresis and blood pressure.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. mferlit1@jhmi.edu
authors.forename: Marcella
authors.initials: M
authors.lastname: Ferlito
authors.forename: William B
authors.initials: WB
authors.lastname: Fulton
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Zauher
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.forename: Charles
authors.initials: C
authors.lastname: Steenbergen
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lowenstein
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002469:Cell Separation; D016232:Endothelins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D051381:Rats; D050987:Vesicle-Associated Membrane Protein 1 / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism*
chemical_list: D016232:Endothelins; D050765:Qa-SNARE Proteins; D050987:Vesicle-Associated Membrane Protein 1; D050988:Vesicle-Associated Membrane Protein 2; D009320:Atrial Natriuretic Factor
references.citation: J Cell Biol. 1964 Oct;23:151-72
references.pmid: 14228508
references.citation: Mol Microbiol. 1994 Jul;13(1):1-8
references.pmid: 7527117
references.citation: J Physiol. 2001 Feb 1;530(Pt 3):417-29
references.pmid: 11158273
references.citation: Cell. 2000 Jan 7;100(1):99-112
references.pmid: 10647935
references.citation: Biophys J. 2001 Nov;81(5):2590-605
references.pmid: 11606273
references.citation: J Physiol. 1996 Aug 1;494 ( Pt 3):641-51
references.pmid: 8865063
references.citation: J Clin Invest. 1987 May;79(5):1325-9
references.pmid: 2952670
references.citation: Mol Biol Cell. 2007 Jan;18(1):24-33
references.pmid: 17065550
references.citation: Ann N Y Acad Sci. 2005 Jun;1047:76-85
references.pmid: 16093486
references.citation: Am J Physiol. 1988 May;254(5 Pt 2):R809-14
references.pmid: 2834970
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8525-9
references.pmid: 10880574
references.citation: Cell. 2003 Feb 21;112(4):519-33
references.pmid: 12600315
references.citation: Nat Struct Mol Biol. 2006 Aug;13(8):748-50
references.pmid: 16845390
references.citation: Blood. 2002 Aug 1;100(3):1081-3
references.pmid: 12130530
references.citation: J Biol Chem. 1997 Mar 7;272(10):6179-86
references.pmid: 9045631
references.citation: Annu Rev Biochem. 1999;68:863-911
references.pmid: 10872468
references.citation: Mol Biol Cell. 1996 Jul;7(7):1075-82
references.pmid: 8862521
references.citation: Can J Physiol Pharmacol. 1991 Oct;69(10):1525-36
references.pmid: 1838022
references.citation: Anat Rec. 1997 May;248(1):70-5
references.pmid: 9143669
references.citation: Basic Res Cardiol. 2004 Mar;99(2):83-9
references.pmid: 14963666
references.citation: J Investig Med. 2005 Nov;53(7):378-84
references.pmid: 16297366
references.citation: Circ Res. 1997 Jul;81(1):86-91
references.pmid: 9201031
references.citation: Am J Physiol. 1995 Sep;269(3 Pt 2):H1165-70
references.pmid: 7573513
references.citation: J Investig Med. 2005 Nov;53(7):371-7
references.pmid: 16297365
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9559-64
references.pmid: 8790369
references.citation: J Neurosci. 1998 Mar 15;18(6):2028-39
references.pmid: 9482790
references.citation: J Mol Cell Cardiol. 2006 Mar;40(3):361-74
references.pmid: 16458920
references.citation: Biochem Biophys Res Commun. 1989 Nov 15;164(3):1431-6
references.pmid: 2531580
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11691-6
references.pmid: 9751727
references.citation: Endocrinology. 1989 Jun;124(6):3109-16
references.pmid: 2524379
references.citation: Am J Physiol. 1999 May;276(5):C1108-14
references.pmid: 10329959
references.citation: Science. 2001 Nov 2;294(5544):1117-22
references.pmid: 11691998
references.citation: Cardiovasc Res. 2005 Oct 1;68(1):8-17
references.pmid: 15993390
references.citation: J Mol Cell Cardiol. 1989 May;21(5):437-40
references.pmid: 2528639
references.citation: Proc Soc Exp Biol Med. 1982 Jun;170(2):133-8
references.pmid: 7201139
references.citation: Am J Physiol. 1994 May;266(5 Pt 2):H1854-63
references.pmid: 8203584
references.citation: Circ Res. 2007 Jul 20;101(2):166-75
references.pmid: 17556655
references.citation: J Mol Cell Cardiol. 1993 May;25(5):509-18
references.pmid: 8377212
references.citation: Curr Probl Cardiol. 2004 Dec;29(12):707-69
references.pmid: 15550914
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11689-94
references.pmid: 16857739
references.citation: J Biol Chem. 1998 Jul 31;273(31):19625-33
references.pmid: 9677389
references.citation: J Cell Sci. 2006 Oct 1;119(Pt 19):3915-25
references.pmid: 16988026
references.citation: Am J Physiol. 1996 Jul;271(1 Pt 2):R109-14
references.pmid: 8760210
references.citation: Biochem Biophys Res Commun. 1989 Sep 15;163(2):701-9
references.pmid: 2476982
references.citation: Life Sci. 1981 Jan 5;28(1):89-94
references.pmid: 7219045
references.citation: Hypertension. 1990 Sep;16(3):301-7
references.pmid: 2144261
references.citation: J Physiol. 2008 Jan 15;586(2):353-66
references.pmid: 18006579
references.citation: J Cell Biol. 1997 Jun 16;137(6):1243-54
references.pmid: 9182659
references.citation: Science. 2006 Aug 4;313(5787):676-80
references.pmid: 16794037
references.citation: Endocrinology. 2004 Nov;145(11):5313-21
references.pmid: 15308619
references.citation: Hypertension. 2003 Jun;41(6):1380-5
references.pmid: 12719444
references.citation: J Biol Chem. 2004 Nov 5;279(45):47125-31
references.pmid: 15339904
references.citation: Biochem Biophys Res Commun. 1988 Nov 30;157(1):330-6
references.pmid: 2461711
references.citation: Cell. 2006 Sep 22;126(6):1175-87
references.pmid: 16990140
references.citation: Heart Fail Rev. 2007 Jun;12(2):131-42
references.pmid: 17440808
references.citation: Endocrinology. 1997 Jul;138(7):3006-15
references.pmid: 9202246
references.citation: Blood. 2003 Sep 1;102(5):1716-22
references.pmid: 12738662
references.citation: Biochem Biophys Res Commun. 2004 Oct 8;323(1):118-24
references.pmid: 15351710