Regulation of atrial natriuretic peptide secretion by a novel Ras-like protein.
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 Ca(2+)-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.
Rybkin
Igor I
II
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Kim
Mi-Sung
MS
Bezprozvannaya
Svetlana
S
Qi
Xiaoxia
X
Richardson
James A
JA
Plato
Craig F
CF
Hill
Joseph A
JA
Bassel-Duby
Rhonda
R
Olson
Eric N
EN
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018631:ras Proteins / Q000378:metabolism*
C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; C524797:RRP17 protein, human; C524798:RRP17 protein, mouse; D009320:Atrial Natriuretic Factor; D019204:GTP-Binding Proteins; D018631:ras Proteins