The regulation of membrane phospholipid asymmetry is involved in the establishment of cell polarity.

点击翻译按钮获取中文摘要

In eukaryotic cells, phospholipids are not randomly distributed between the lipid bilayers. Instead, phospholipids are asymmetrically arranged between two leaflets of the plasma membrane. The physiological functions of an asymmetric lipid arrangement are unclear. A membrane protein family, CdcS0 family, which we have recently identified as a factor involved in the establishment of cell polarity in Saccharomyces cerevisiae, is non-catalytic subunits of aminophospholipid translocases. We have investigated cellular functions of phospholipid translocases, using Cdc50 family mutants and demonstrated as follows.1. We analyzed the mutants that lacked Lem3, a member of Cdc50 family that functions in the plasma membrane and showed that the activities of phospholipid translocases in the plasma membrane are required for the transition from the apical growth phase to the isotropic growth phase during the bud growth. These findings exhibited that the internalization of phosphatidylethanolamine (PE) … More specifically exposed to the outer leaflet at the site of polarized growth to the inner leaflet catalyzed by phospholipid translocases is necessary to the transition to the isotropic growth. We also demonstrated that a small GTPase Cdc42 is implicated in this process and that the translocation of PE from the outer leaflet to the inner leaflet may activate GTPase-activating protein (GAP), a negative regulator of Cdc42.2. The mutants that lacked Cdc50 (cdc50Δ), which predominantly functions in TGN/endosomes, showed cold-sensitive cell-cycle arrest with deficiencies in establishment of cell polarity. We screened for mutations that suppress the growth defect of the cdc50Δ mutant at low temperatures and identified a new gene, YMR0101w. The disruption mutation of the YMRO1Ow gene efficiently suppressed the defects in establishing cell polarity and endocytic recycling observed in the cdc50Δ mutant. Thus, we showed that Ymr0101w is involved in the functions of the phospholipid translocase consisting of Cdc50 and its partner Drs2. Less