VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes

Ferlito, Marcella; Fulton, William B.; Zauher, Mohamed A.; Marbán, Eduardo; Steenbergen, Charles; Lowenstein, Charles J.

doi:10.1016/j.yjmcc.2010.08.020

« Previous Next »Journal of Molecular and Cellular Cardiology
Volume 49, Issue 5 , Pages 791-800, November 2010

VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes

Marcella Ferlito
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Corresponding author. The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Tel.: +1-410-502-5982.
William B. Fulton
- Department of Pediatric Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mohamed A. Zauher
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Eduardo Marbán
- Cedars-Sinai Heart Institute, Cedars Sinai, Los Angeles, CA, USA
Charles Steenbergen
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Charles J. Lowenstein
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- The University of Rochester Medical Center, Rochester, NY 14534, USA

Received 7 January 2010; received in revised form 19 August 2010; accepted 20 August 2010. published online 30 August 2010.

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, 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.

Research Highlights

►ANP is released from cardiac myocytes by exocytosis. ►Cardiac myocytes express a subset of SNARE proteins. ►SNARE proteins VAMP-1, VAMP-2, and syntaxin-4 regulate ANP exocytosis.

Keywords: Exocytosis, Granule, Trafficking, Hypertension, Secretion, Nitric oxide, N-ethylmaleimide sensitive factor