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Published online
doi:10.1083/jcb.200707101
The Journal of Cell Biology, Vol. 179, No. 3, 527-537
The Rockefeller University Press, 0021-9525 $30.00
© Rybkin et al.
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Article

Regulation of atrial natriuretic peptide secretion by a novel Ras-like protein



Igor I. Rybkin1, Mi-Sung Kim1, Svetlana Bezprozvannaya1, Xiaoxia Qi1, James A. Richardson2, Craig F. Plato4, Joseph A. Hill3, Rhonda Bassel-Duby1, and Eric N. Olson1

1 Department of Molecular Biology, 2 Department of Pathology, and 3 Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
4 Gilead-Colorado, Westminster, CO 80021

Correspondence to Eric N. Olson: eric.olson{at}utsouthwestern.edu

Atrial cardiomyocytes, neurons, and endocrine tissues secrete neurotransmitters and peptide hormones via large dense-core vesicles (LDCVs). We describe a new member of the Ras family of G-proteins, named RRP17, which is expressed specifically in cardiomyocytes, neurons, and the pancreas. RRP17 interacts with Ca2+-activated protein for secretion-1 (CAPS1), one of only a few proteins known to be associated exclusively with LDCV exocytosis. Ectopic expression of RRP17 in cardiomyocytes enhances secretion of atrial natriuretic peptide (ANP), a regulator of blood pressure and natriuresis. Conversely, genetic deletion of RRP17 in mice results in dysmorphic LDCVs, impaired ANP secretion, and hypertension. These findings identify RRP17 as a component of the cellular machinery involved in regulated secretion within the heart and potential mediator of the endocrine influence of the heart on other tissues.

Abbreviations used in this paper: ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; C2, calcium binding domain; CAPS1, calcium-activated protein for secretion 1; CNP, C-type natriuretic peptide; DCV, dense-core vesicle; DNP, dendroaspis natriuretic peptide; GNB, guanine nucleotide binding domain; LDCV, large dense-core vesicles; MHD, munc homology domain; NP, natriuretic peptide; PH, pleckstrin homology; RRP17, Ras-related protein 17; TAB, thoracic aortic banding.


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