BACKGROUND: Phospholamban is a reversible inhibitor of the Ca(2+)-ATPase of the cardiac sarcoplasmic reticulum (SR) and contributes to the regulation of heart muscle contractility. Because only the monomeric form, not the pentameric form, of phospholamban inhibits the Ca2+-pumping activity of the SR, it is important to understand the dynamic equilibrium between these 2 forms. METHODS AND RESULTS: The effects of various detergents and phospholipids on the oligomeric state of phospholamban were examined. Among the detergents examined, 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) stabilized the pentameric form whereas octylglucoside was an effective inducer of dissociation into the monomer. On the basis of these properties of the 2 detergents, the effects of various phospholipids on the oligomeric state of phospholamban with the use of mixed micelles containing octylglucoside or CHAPS were examined. Among the 8 phospholipids examined, phosphatidic acid was an effective inducer of pentamer dissociation, whereas the other phospholipids exhibited pentamer-stabilizing activity. Lysophosphatidylcholine, lysophosphatidylethanolamine, and phosphatidylglycerol were highly effective stabilizers of the pentamer. CONCLUSIONS: The phospholipids in the SR membrane are important determinants of the equilibrium between the monomeric and pentameric forms of this protein. The results suggest that the metabolism of phospholipids in the cardiac SR may contribute to regulation of heart muscle contractility by shifting this equilibrium.
BACKGROUND: Phospholamban is a reversible inhibitor of the Ca(2+)-ATPase of the cardiac sarcoplasmic reticulum (SR) and contributes to the regulation of heart muscle contractility. Because only the monomeric form, not the pentameric form, of phospholamban inhibits the Ca2+-pumping activity of the SR, it is important to understand the dynamic equilibrium between these 2 forms. METHODS AND RESULTS: The effects of various detergents and phospholipids on the oligomeric state of phospholamban were examined. Among the detergents examined, 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) stabilized the pentameric form whereas octylglucoside was an effective inducer of dissociation into the monomer. On the basis of these properties of the 2 detergents, the effects of various phospholipids on the oligomeric state of phospholamban with the use of mixed micelles containing octylglucoside or CHAPS were examined. Among the 8 phospholipids examined, phosphatidic acid was an effective inducer of pentamer dissociation, whereas the other phospholipids exhibited pentamer-stabilizing activity. Lysophosphatidylcholine, lysophosphatidylethanolamine, and phosphatidylglycerol were highly effective stabilizers of the pentamer. CONCLUSIONS: The phospholipids in the SR membrane are important determinants of the equilibrium between the monomeric and pentameric forms of this protein. The results suggest that the metabolism of phospholipids in the cardiac SR may contribute to regulation of heart muscle contractility by shifting this equilibrium.
Authors: Daniel Koch; Alexander Alexandrovich; Florian Funk; Ay Lin Kho; Joachim P Schmitt; Mathias Gautel Journal: Cell Rep Date: 2021-07-27 Impact factor: 9.995