TY - JOUR
T1 - VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes
AU - Ferlito, Marcella
AU - Fulton, William B.
AU - Zauher, Mohamed A.
AU - Marbán, Eduardo
AU - Steenbergen, Charles
AU - Lowenstein, Charles J.
N1 - Funding Information:
Supported by grants from the NIH ( R01 HL63706 , R01 HL074061 , P01 HL65608 , P01 HL56091 ), and the Paul N. Yu Professorship to CJL. Supported by grants from the AHA ( 0830395N ) to MF.
PY - 2010/11
Y1 - 2010/11
N2 - 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, sytntaxin-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.
AB - 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, sytntaxin-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.
KW - Exocytosis
KW - Granule
KW - Hypertension
KW - N-ethylmaleimide sensitive factor
KW - Nitric oxide
KW - Secretion
KW - Trafficking
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U2 - 10.1016/j.yjmcc.2010.08.020
DO - 10.1016/j.yjmcc.2010.08.020
M3 - Article
C2 - 20801128
AN - SCOPUS:77957231334
SN - 0022-2828
VL - 49
SP - 791
EP - 800
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 5
ER -