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

膜磷脂不对称性的调节参与细胞极性的建立。

基本信息

批准号：
17570151
负责人：
KAMADA Konomi
金额：
$ 2.24万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570151/
关键词：
cell polarity budding yeast lipid bilayer phospholipid translocation vesicular trafficking cell biology Cdc42 Cdc42

项目摘要

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

在真核细胞中，磷脂并不是随机分布在脂双层之间。相反，磷脂不对称地排列在质膜的两个小叶之间。不对称脂质排列的生理功能尚不清楚。我们新近发现的一个膜蛋白家族--CDcS0家族，是氨基磷脂转位酶的非催化亚基，是酿酒酵母细胞极性形成的一个相关因子。我们利用CDC50家族突变体研究了磷脂转位酶的细胞功能，并证明如下。我们对缺乏Lem3的突变体进行了分析，发现在芽的生长过程中，质膜上的磷脂转运酶的活性是从顶端生长阶段向各向同性生长阶段过渡所必需的。这些发现表明，磷脂酰乙醇胺(PE)…的内化更具体地说，暴露在外叶的极化生长部位到内叶的磷脂转位酶的催化作用是向各向同性生长过渡所必需的。我们还证明了一个小的GTP酶CDC42参与了这一过程，并且PE从外叶到内叶的移位可能激活了CDC42.2的负调节因子GTP酶激活蛋白(GAP)。缺乏CDC50(CDC50Δ)的突变体表现出对冷敏感的细胞周期停滞，并缺乏细胞极性的建立。我们筛选了在低温下抑制CDC50Δ突变体生长缺陷的突变，并鉴定了一个新基因YMR0101w。YMRO10w基因的中断突变有效地抑制了在CDC50Δ突变体中观察到的在建立细胞极性和内吞循环方面的缺陷。因此，我们证明Ymr0101w参与了由CDC50及其伙伴Drs2组成的磷脂转位酶的功能。较少