Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Mol Cell Cardiol. 2010 Nov;49(5):791-800. doi: 10.1016/j.yjmcc.2010.08.020. Epub 2010 Aug 27.
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.
心钠肽（ANP）是由心肌细胞释放的一种调节血压和利钠的肽。然而，控制心肌细胞释放 ANP 的分子机制尚不清楚。我们现在确定了调节心房肌细胞 ANP 释放的三个外排机制组件。我们发现心肌细胞表达 N-乙基马来酰亚胺敏感因子（NSF）、可溶性 NSF 附着蛋白（α-SNAP）和 SNAP 受体（SNAREs）。此外，我们发现特定的 SNARE 分子 VAMP-1 和 VAMP-2 均与 ANP 共沉淀和共定位。此外，一种 SNARE 分子 syntaxin-4 部分与 ANP 共沉淀，部分与 ANP 共定位。此外，这三种 SNARE 分子 syntaxin-4、VAMP-1 和 VAMP-2 在心肌细胞内形成 SNARE 复合物。最后，敲低 VAMP-1、VAMP-2 或 syntaxin-4 可阻止 ANP 的调节性释放。相比之下，沉默 VAMP-3 对 ANP 释放没有影响。我们的数据表明，三个特定的 SNARE 调节心肌细胞 ANP 的胞吐作用。修饰外排机制的途径可能会影响利钠和血压。
