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Roles for phospholipid asymmetry in cell polarity

磷脂不对称在细胞极性中的作用

基本信息

批准号：
15370081
负责人：
TANAKA Kazuma
金额：
$ 7.62万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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.

细胞极性是所有真核细胞的基本细胞功能。它在疾病中也很重要：癌细胞显示细胞极性异常。另一方面，在真核细胞的质膜中，已知细胞外小叶和细胞内小叶之间的脂质组成是不同的。我们已经确定Cdc 50是酵母中调节细胞极性形成的基因。最近，我们发现Cdc 50蛋白与Drs 2 p型ATP酶形成复合物，该复合物将磷脂从细胞外转移到细胞内小叶。我们还表明，麦角固醇和磷脂的不对称性调节肌动蛋白细胞骨架的极化组织，我们已经发表了这些结果。今年，我们进一步取得了以下成果。(1)我们已经表明，Cdc 50-Drs 2复合物及其类似物调节内吞再循环途径。此外，我们发现Cdc 50-Drs 2的功能受Rab家族小GTdR Ypt 31/32及其效应子Rcy 1（Tanaka和Kamada）的调节。(2)我们已经证明，Cdc 50-Drs 2参与了由Arf 1小GTbR调控的囊泡出芽。Gga蛋白在Arf 1的这一功能中似乎起着效应器的作用（Tanaka and Yamamoto）。基于这些观察，我们提出磷脂不对称性在囊泡从内体出芽的过程中起着重要作用。因此，我们今年也取得了稳步进展。