Roles for phospholipid asymmetry in cell polarity

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Cell polarity is a fundamental cell function to all eukaryotic cells. It is also important in diseases : cancer cells display abnormality in cell polarity. On the other hand, in the plasma membrane in eukaryotic cells, it is known that lipid composition is different between extracellular and intracellular leaflets.We had identified Cdc50 as a gene that regulates formation of cell polarity in yeast. Recently, we showed that the Cdc50 protein forms a complex with the Drs2 p-type ATPase that translocates phospholipids from the extracellular to intracellular leaflet. We have also shown that both ergosterol and phospholipid asymmetry regulate polarized organization of the actin cytoskeleton, and we have published these results. This year, we have further obtained following results.(1) We have shown that the Cdc50-Drs2 complex and its analogous complexes regulate the endocytic recycling pathway. In addition, we found that the functions of Cdc50-Drs2 are regulated by the Rab family small GTPase Ypt31/32 and its effector Rcy1 (Tanaka and Kamada).(2) We have demonstrated that Cdc50-Drs2 is involved in vesicle budding regulated by the Arf1 small GTPase. It seemed that Gga proteins serve as effectors in this function of Arf1 (Tanaka and Yamamoto).Based on these observations, we propose that phospholipid asymmetry plays an important role in the process of vesicle budding from endosomes. Thus, we have also made steady progress this year.