Phospholipase Cε Hydrolyzes Perinuclear Phosphatidylinositol 4-Phosphate to Regulate Cardiac Hypertrophy
| Autor: | David I. Yule, Huan Wang, Jinjiang Pang, Alan V. Smrcka, Keigan M. Park, Lianghui Zhang, Burns C. Blaxall, Sundeep Malik |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Phosphatidylinositol 4-phosphate Nuclear Envelope Heart Ventricles Golgi Apparatus Cardiomegaly Phospholipase Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound symbols.namesake Mice 0302 clinical medicine Phosphoinositide Phospholipase C Phosphatidylinositol Phosphates Phosphoinositide phospholipase C Animals Myocytes Cardiac Phosphatidylinositol Nuclear protein Aorta 030304 developmental biology Diacylglycerol kinase 0303 health sciences Biochemistry Genetics and Molecular Biology(all) Kinase Heart Golgi apparatus Cell biology Rats chemistry Biochemistry symbols cardiovascular system GTP-Binding Protein alpha Subunits Gq-G11 030217 neurology & neurosurgery Signal Transduction |
| Popis: | SummaryPhospholipase Cε (PLCε) is a multifunctional enzyme implicated in cardiovascular, pancreatic, and inflammatory functions. Here we show that conditional deletion of PLCε in mouse cardiac myocytes protects from stress-induced pathological hypertrophy. PLCε small interfering RNA (siRNA) in ventricular myocytes decreases endothelin-1 (ET-1)-dependent elevation of nuclear calcium and activation of nuclear protein kinase D (PKD). PLCε scaffolded to muscle-specific A kinase-anchoring protein (mAKAP), along with PKCε and PKD, localizes these components at or near the nuclear envelope, and this complex is required for nuclear PKD activation. Phosphatidylinositol 4-phosphate (PI4P) is identified as a perinuclear substrate in the Golgi apparatus for mAKAP-scaffolded PLCε. We conclude that perinuclear PLCε, scaffolded to mAKAP in cardiac myocytes, responds to hypertrophic stimuli to generate diacylglycerol (DAG) from PI4P in the Golgi apparatus, in close proximity to the nuclear envelope, to regulate activation of nuclear PKD and hypertrophic signaling pathways. |
| Databáze: | OpenAIRE |
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