Identification of phospholipid translocase and its role in cell polarity formation.

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It is well established that phospholipids in biological membranes are distributed asymmetrically between the inner and outer leaflets of the lipid bilayer. Although recent studies have shown that the transbilayer lipid asymmetry is generated and controlled by a family of specific lipid transport proteins, the physiological role of the lipid asymmetry remains largely unknown. Over the past decade, we have established a series of phospholipid-binding probes and mammalian cell mutants defective in phospholipid biosynthesis. These probes and mutants have provided useful tools to study the molecular motion and the cellular function of membrane phospholipids.In the final stage of cell division, cytokinesis constricts and then seals the plasma membrane between the two daughter cells. The constriction is powered by a contractile ring of actin, and scission involves a fusion or rearrangement of the lipid bilayer of the cell membrane. Using phospholipid-specific binding probes that we have gener … More ated over the past decade, we found that the lipid phosphatidylethanolamine (PE), which normally resides in the inner leaflet of the bilayer, was exposed onto the outer leaflet of the cleavage furrow. Subsequent analyses, using the phospholipid-binding probes and mutant cells defective in PE synthesis, have shown that this surface exposure of PE on the cleavage furrow is needed to coordinate the reorganization of the actin cytoskeleton and the plasma membrane during cytokinesis.To identify the molecules involved in the lipid-cytoskeleton coordination, we have isolated budding yeast mutants that have a defective in the transbilayer movement of phospholipids. A gene, designated as ROS3, was identified as a regulator of transbilayer relocation of PE on plasma membrane. ROS3 encodes a novel transmembrane protein present on plasma membrane. Disruption of ROS3 resulted in defects in morphology and formation of cortical actin patch. Overexpression of Ros3p led to multibud formation. Since Ros3p homologue is strongly expressed in some mammalian tissues such as brain and epithelial cells, Ros3p may play a general role in possible cross-talks between the cytoskeleton and membrane lipids that are required for proper cell division as well as cell polarity formation. Less