Synthesis of sphingolipids with very long chain fatty acids but not ergosterol is required for routing of newly synthesized plasma membrane ATPase to the cell surface of yeast
Synthesis of sphingolipids with very long chain fatty acids but not ergosterol is required for routing of newly synthesized plasma membrane ATPase to the cell surface of yeast
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DOI：
10.1074/jbc.m413472200
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发表时间：
2005-06-10
影响因子：
4.8
通讯作者：
Schneiter, R
中科院分区：
文献类型：
--
作者：
Gaigg, B;Timischl, B;Schneiter, R
质子泵H+-ATPase，Pma1p，是酿酒酵母质膜上含量丰富、寿命极长的多态蛋白。Pma1p是分泌途径的主要载体，是研究质膜生物发生的良好模型。我们先前已经证明，在一个elo3 Delta突变体中，新合成的Pma1p被错误地定位到液泡中，它影响了神经酰胺结合的C26超长链脂肪酸的合成(Eisenkolb，M.，Zenzmaier，C.，Leitner，E.和Schneiter，R.(2002)Mol。比奥尔。细胞13,4414-4428)，现在描述更详细的脂类在Pma1p生物发生中的作用的分析。值得注意的是，阻止固醇生物合成的各个步骤，完全阻止固醇合成，或者用外部提供的麦角固醇甚至胆固醇取代内部合成的麦角甾醇，都不会影响Pma1p的生物合成或它与抗洗涤剂膜结构域(脂“筏”)的联系。然而，鞘脂合成的障碍或神经酰胺结合的C26超长链脂肪酸的合成的任何扰动都会导致新合成的Pma1p错误地定位到液泡。错误定位与缺乏新合成的Pma1p来获得洗涤剂抗性有关，这表明具有非常长的酰基链的鞘磷脂影响Pma1p到细胞表面的分选。
The proton pumping H+- ATPase, Pma1p, is an abundant and very long-lived polytopic protein of the Saccharomyces cerevisiae plasma membrane. Pma1p constitutes a major cargo of the secretory pathway and thus serves as an excellent model to study plasma membrane biogenesis. We have previously shown that newly synthesized Pma1p is mistargeted to the vacuole in an elo3 Delta mutant that affects the synthesis of the ceramide-bound C26 very long chain fatty acid (Eisenkolb, M., Zenzmaier, C., Leitner, E., and Schneiter, R. ( 2002) Mol. Biol. Cell 13, 4414-4428) and now describe a more detailed analysis of the role of lipids in Pma1p biogenesis. Remarkably, a block at various steps of sterol biosynthesis, a complete block in sterol synthesis, or the substitution of internally synthesized ergosterol by externally supplied ergosterol or even by cholesterol does not affect Pma1p biogenesis or its association with detergent-resistant membrane domains (lipid "rafts"). However, a block in sphingolipid synthesis or any perturbation in the synthesis of the ceramide-bound C26 very long chain fatty acid results in mistargeting of newly synthesized Pma1p to the vacuole. Mistargeting correlates with a lack of newly synthesized Pma1p to acquire detergent resistance, suggesting that sphingolipids with very long acyl chains affect sorting of Pma1p to the cell surface.