Effects of Regulator of G Protein Signaling 19 (RGS19) on Heart Development and Function

• Published in: The Journal of biological chemistry Vol. 285; no. 37; pp. 28627 - 28634
• Main Authors: Ji, Young Rae, Kim, Myoung Ok, Kim, Sung Hyun, Yu, Dong Hun, Shin, Mi Jung, Kim, Hei Jung, Yuh, Hyung Soo, Bae, Ki Beom, Kim, Jae Young, Park, Hum Dai, Lee, Sang Gyu, Hyun, Byung Hwa, Ryoo, Zae Young
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-09-2010; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Bioenergetics; Bone Morphogenetic Protein 4 - genetics; Bone Morphogenetic Protein 4 - metabolism; Cell Biology; Cell Differentiation; Cell Line, Tumor; Development Differentiation; Development Differentiation/ Organ; Developmental Biology; G Proteins; Gene/Transgene; GTP-Binding Protein alpha Subunits - genetics; GTP-Binding Protein alpha Subunits - metabolism; Heart; Heart - embryology; Heart Failure - genetics; Heart Failure - metabolism; Heart Septal Defects - genetics; Heart Septal Defects - metabolism; MEF2 Transcription Factors; Mice; Mice, Transgenic; Myocytes, Cardiac - metabolism; Myogenic Regulatory Factors - genetics; Myogenic Regulatory Factors - metabolism; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Natriuretic Peptide, Brain - genetics; Natriuretic Peptide, Brain - metabolism; RGS Proteins - genetics; RGS Proteins - metabolism; Signal Transduction; Tissue/Organ Systems/Heart; Wnt Proteins - genetics; Wnt Proteins - metabolism; Heart; Gene/Transgene; Bioenergetics; G Proteins; Development Differentiation; Development Differentiation/ Organ; Tissue/Organ Systems/Heart
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.073718

Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/β-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which has Gα subunits with GTPase activity, inhibits the Wnt/β-catenin signal through inactivation of Gαo. In the present study, the effects of RGS19 on mouse cardiac development were observed. In P19 teratocarcinoma cells with RGS19 overexpression, RGS19 inhibited cardiomyocyte differentiation by blocking the Wnt signal. Additionally, several genes targeted by Wnt were down-regulated. For the in vivo study, we generated RGS19-overexpressing transgenic (RGS19 TG) mice. In these transgenic mice, septal defects and thin-walled ventricles were observed during the embryonic phase of development, and the expression of cardiogenesis-related genes, BMP4 and Mef2C, was reduced significantly. RGS19 TG mice showed increased expression levels of brain natriuretic peptide and β-MHC, which are markers of heart failure, increase of cell proliferation, and electrocardiogram analysis shows abnormal ventricle repolarization. These data provide in vitro and in vivo evidence that RGS19 influenced cardiac development and had negative effects on heart function.