Phospholipid flippases and Sfk1p, a novel regulator of phospholipid asymmetry, contribute to low permeability of the plasma membrane

• DOI: 10.1091/mbc.e17-04-0217
• Publication Date: 2018-03-14T17:11:20Z
• Authors: Tetsuo Mioka; Konomi Fujimura-K...; Nahiro Mizugaki; Takuma Kishimoto; Takamitsu Sano; Hitoshi Nunome; David E. Williams; Raymond J. Andersen; Kazuma Tanaka
• Keywords: Flippase; Phosphatidylethanolamine; Phospholipid transfer protein; Cell membrane

Phospholipid flippase (type 4 P-type ATPase) plays a major role in the generation of phospholipid asymmetry eukaryotic cell membranes. Loss Lem3p-Dnf1/2p flippases leads to exposure phosphatidylserine (PS) and phosphatidylethanolamine (PE) on surface yeast, resulting sensitivity PS- or PE-binding peptides. We isolated Sfk1p, conserved membrane protein TMEM150/FRAG1/DRAM family, as multicopy suppressor this sensitivity. Overexpression SFK1 decreased PS/PE lem3Δ mutant cells. Consistent with this, sfk1Δ double cells exposed more than mutant. Sfk1p was previously implicated regulation phosphatidylinositol-4 kinase Stt4p, but effect independent Stt4p. Surprisingly, did not facilitate flipping instead repressed it, even under ATP-depleted conditions. propose that negatively regulates transbilayer movement phospholipids irrespective directions. In addition, we showed permeability plasma dramatically elevated comparison corresponding single mutants. Interestingly, total ergosterol Our results suggest is required for maintenance low permeability.