A novel factor OPT2 mediates exposure of phospholipids during cellular adaptation to altered lipid asymmetry

Abstract

Plasma membrane lipid asymmetry is important for various membrane-associated functions and regulated by membrane proteins termed flippases and floppases. The Rim101 pathway senses altered lipid asymmetry in the yeast plasma membrane. The mutant lem3Δ cells, in which lipid asymmetry is disturbed due to the inactivation of the plasma membrane flippases, showed a severe growth defect when the Rim101 pathway was impaired. To identify factors involved in the Rim101 pathway-dependent adaptation to altered lipid asymmetry, we performed DNA microarray analysis and found that Opt2 induced by the Rim101 pathway plays an important role in the adaptation to altered lipid asymmetry. Biochemical investigation of Opt2 revealed its localization to the plasma membrane and the Golgi apparatus and provided several lines of evidence for the Opt2-mediated exposure of phospholipids. In addition, Opt2 was found to be required for the maintenance of vacuole morphology and polarized cell growth. These results suggest that Opt2 is a novel factor involved in cell homeostasis by regulating lipid asymmetry.