| First Author | Zhang L | Year | 2013 |
| Journal | Cell | Volume | 153 |
| Issue | 1 | Pages | 216-27 |
| PubMed ID | 23540699 | Mgi Jnum | J:197247 |
| Mgi Id | MGI:5491968 | Doi | 10.1016/j.cell.2013.02.047 |
| Citation | Zhang L, et al. (2013) Phospholipase Cepsilon hydrolyzes perinuclear phosphatidylinositol 4-phosphate to regulate cardiac hypertrophy. Cell 153(1):216-27 |
| abstractText | Phospholipase Cepsilon (PLCepsilon) is a multifunctional enzyme implicated in cardiovascular, pancreatic, and inflammatory functions. Here we show that conditional deletion of PLCepsilon in mouse cardiac myocytes protects from stress-induced pathological hypertrophy. PLCepsilon 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). PLCepsilon scaffolded to muscle-specific A kinase-anchoring protein (mAKAP), along with PKCepsilon 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 PLCepsilon. We conclude that perinuclear PLCepsilon, 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. |
