Phospholipid methylation in skeletal muscle membranes

Abstract

Phospholipid methylation is thought to modulate such vital cellular processes as calcium transport, receptor function, and membrane microviscosity. As these processes are fundamental to the function of muscle cells and are thought to be altered in disease states, we have characterized several features of phospholipid methylation reactions in skeletal muscle and have defined appropriate assay conditions. In rat leg muscle, methyltransferase activity was assayed radiometrically by measuring the incorporation of methyl groups from S-adenosyl-L-[methyl-3H]methionine into membrane phospholipids, the methylated derivatives of which were separated by thin-layer chromatography. Contrary to previous investigations of whole muscle, phospholipid methyltransferase activity was clearly present in skeletal muscle membranes, being highly localized in sarcoplasmic reticulum and present to a lesser extent in sarcolemma. Both the reaction products and the reaction kinetics were consistent with sequential methylation of phospholipids by two methyltransferase enzymes. S-adenosylhomocysteine and its analogues were potent inhibitors of phospholipid methylation in sarcoplasmic reticulum. The predominant localization of phospholipid methyltransferase activity in sarcoplasmic reticulum suggests that its functional role in skeletal muscle may be in calcium transport.