Document Type
Article
Publication Date
3-15-2015
Abstract
We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. Finally, blocking Gβγ at the Golgi or PM blocked ET-1-dependent cardiomyocyte hypertrophy. These data indicate that Gβγ regulation of the perinuclear Golgi PI4P pathway and a separate pathway at the PM is required for ET-1-stimulated hypertrophy, and the efficacy of Gβγ inhibition in preventing heart failure maybe due in part to its blocking both these pathways.
Recommended Citation
Malik, S; deRubio, R G; Trembley, M; Irannejad, R; Wedegaertner, Philip B; and Smrcka, A V, "G protein βγ subunits regulate cardiomyocyte hypertrophy through a perinuclear Golgi phosphatidylinositol 4-phosphate hydrolysis pathway." (2015). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 85.
https://jdc.jefferson.edu/bmpfp/85
PubMed ID
25609085
Comments
This article has been peer reviewed. It was published in: Molecular Biology of the Cell.
Volume 26, Issue 6, 15 March 2015, Pages 1188-1198.
The published version is available at DOI: 10.1091/mbc.E14-10-1476
Copyright © 2015 Malik et al.