Cross talk between sphingolipids and glycerophospholipids in the establishment of plasma membrane asymmetry
Cross talk between sphingolipids and glycerophospholipids in the establishment of plasma membrane asymmetry
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DOI：
10.1091/mbc.e04-06-0458
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发表时间：
2004-11-01
影响因子：
3.3
通讯作者：
Igarashi, Y
中科院分区：
文献类型：
--
作者：
Kihara, A;Igarashi, Y
甘油磷脂和鞘磷脂不对称地分布在脂双层的两个小叶之间。最近的研究表明，某些P型ATPase和ATP结合盒(ABC)转运体分别参与甘油磷脂的内向运动(FliP)和向外运动(Flop)。在对植鞘糖苷(PHS)抗性酵母突变体的研究中，我们分离到了参与药物外排和磷脂酰乙醇胺倒挂的ABC转运蛋白PDR5的突变体。Pdr5突变体的狮身人面肌长链碱基外流增加。遗传分析表明，pdr5突变体表现出的PHS抗性表型依赖于Rsb1p，Rsb1p是一种假定的LCB特异性转运蛋白/易位酶。我们发现Rsb1p在pdr5突变体中的表达增加。我们还证明了RSB1的表达受转录因子Pdr1p的控制。参与甘油磷脂翻转的基因，包括ROS3、DNF1和DNF2，Rsb1p的表达也在突变体中增强。这些结果表明，甘油磷脂不对称改变诱导了Rsb1p的表达。相反，Rsb1p的过表达导致荧光标记的甘油磷脂的翻转增加和触发器减少。因此，鞘磷脂和甘油磷脂之间似乎存在着维持质膜功能脂不对称的串扰。
Glycerophospholipids and sphingolipids are distributed asymmetrically between the two leaflets of the lipid bilayer. Recent studies revealed that certain P-type ATPases and ATP-binding cassette (ABC) transporters are involved in the inward movement (flip) and outward movement (flop) of glycerophospholipids, respectively. In this study of phytosphingosine (PHS)-resistant yeast mutants, we isolated mutants for PDR5, an ABC transporter involved in drug efflux as well as in the flop of phosphatidylethanolamine. The pdr5 mutants exhibited an increase in the efflux of sphingoid long-chain bases (LCBs). Genetic analysis revealed that the PHS-resistant phenotypes exhibited by the pdr5 mutants were dependent on Rsb1p, a putative LCB-specific transporter/translocase. We found that the expression of Rsb1p was increased in the pdr5 mutants. We also demonstrated that expression of RSB1 is under the control of the transcriptional factor Pdr1p. Expression of Rsb1p also was enhanced in mutants for the genes involved in the flip of glycerophospholipids, including ROS3, DNF1, and DNF2. These results suggest that altered glycerophospholipid asymmetry induces the expression of Rsb1p. Conversely, overexpression of Rsb1p resulted in increased flip and decreased flop of fluorescence-labeled glycerophospholipids. Thus, there seems to be cross talk between sphingolipids and glycerophospholipids in maintaining the functional lipid asymmetry of the plasma membrane.