Yeast sphingolipids do not need to contain very long chain fatty acids
Yeast sphingolipids do not need to contain very long chain fatty acids
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DOI：
10.1042/bj20061128
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发表时间：
2007-01-01
影响因子：
4.1
通讯作者：
Conzelmann, Andreas
中科院分区：
文献类型：
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作者：
Cerantola, Vanessa;Vionnet, Christine;Conzelmann, Andreas
超长链脂肪酸（VLCFAs）的合成和二氢鞘氨醇（DHS）的生物合成都对酿酒酵母至关重要。VLCFAs和DHS的球茎通过Lag1p（长寿保证基因1）/Lac1p（长寿保证基因同源基因1）/Lip1p （Lag1p/Lac1p相互作用蛋白）神经酰胺合成酶合成神经酰胺。LAG1和LAC1是多余的，但LIP1是必不可少的。在这里，我们发现缺乏所有已知内源性神经酰胺合成途径的4个Delta （lag1 Delta lac1 Delta ypc1 Delta ydc1 Delta）细胞是不可存活的，但可以通过小鼠lag1同源物Lass5的表达来拯救。4 δ神经酰胺合成酶活性。Lass5细胞仅利用C和C-18脂肪酸，不需要Lip1p的帮助，Lip1p是Lag1p/Lac1p的重要辅助因子。高效液相色谱-电喷雾-质谱分析表明，4 δ δ肌醇磷酸化神经酰胺（IPCs）。在Lass5中，超长链脂肪酸（C-26和C-24）占< 1%，而不是正常的97%。尽管如此，IPCs与4 Delta的糖基磷脂酰肌醇锚结合。Lass5在TLC上表现出正常的流动性，神经酰胺和筏依赖的Gas1p（糖磷脂锚定表面蛋白）从内质网到高尔基体的运输几乎保持正常。此外，C-24:0脂肪酸的生物合成仍然是必不可少的。因此，C-24:0和二氢鞘氨醇都是酵母细胞存活所必需的，即使它们利用C-16和C-18脂肪酸进行鞘脂生物合成。
Synthesis of VLCFAs (very long chain fatty acids) and biosynthesis of DHS (dihydrosphingosine) both are of vital importance for Saccharomyces cerevisiae. The bulb, of VLCFAs and DHS are used for ceramide synthesis by the Lag1p (longevity-assurance gene 1)/Lac1p (longevity-assurance gene cognate 1)/Lip1p (Lag1p/Lac1p interacting protein) ceramide synthase. LAG1 and LAC1 are redundant but LIP1 isessential. Here we show that 4 Delta (lag1 Delta lac1 Delta ypc1 Delta ydc1 Delta) cells devoid of all known endogenous ceramide synthesis pathways are unviable but can be rescued by the expression of Lass5, a mouse LAG1 homologue. Ceramide synthase activity of 4 Delta. Lass5 cells only utilizes C, and C-18 fatty acids and does not require the help of Lip1p, an essential cofactor of Lag1p/Lac1p. HPLC-electrospray ionization-MS/MS analysis demonstrated that in IPCs (inositolphosphorylceramides) of 4 Delta. Lass5, the very long chain fatty acids (C-26 and C-24) account for < I % instead of the normal > 97 %. Notwithstanding, IPCs incorporated into glycosylphosphatidylinositol anchors of 4 Delta.Lass5 show normal mobility on TLC and the ceramide and raft-dependent traffic of Gas1p (glycophospholipid-anchored surface protein) from endoplasmic reticulum to Golgi remains almost normal. Moreover, the biosynthesis of C-24:0 fatty acids remains essential. Thus, C-24:0 and dihydrosphingosine are both necessary for survival of yeast cells even if they utilize C-16 and C-18 fatty acids for sphingolipid biosynthesis.