VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes.
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.
Ferlito
Marcella
M
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. mferlit1@jhmi.edu
Fulton
William B
WB
Zauher
Mohamed A
MA
Marbán
Eduardo
E
Steenbergen
Charles
C
Lowenstein
Charles J
CJ
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*
D016232:Endothelins; D050765:Qa-SNARE Proteins; D050987:Vesicle-Associated Membrane Protein 1; D050988:Vesicle-Associated Membrane Protein 2; D009320:Atrial Natriuretic Factor
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