Saccharomyces cerevisiae CWH43 is involved in the remodeling of the lipid moiety of GPI anchors to ceramides.
Saccharomyces cerevisiae CWH43 is involved in the remodeling of the lipid moiety of GPI anchors to ceramides.
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DOI：
10.1091/mbc.e07-05-0482
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发表时间：
2007-11
影响因子：
3.3
通讯作者：
Mariko Umemura;Morihisa Fujita;T. Yoko-o;A. Fukamizu;Y. Jigami
中科院分区：
文献类型：
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作者：
Mariko Umemura;Morihisa Fujita;T. Yoko-o;A. Fukamizu;Y. Jigami
糖基磷脂酰肌醇（GPI）锚定蛋白在其生物合成过程中受到脂质重塑。在酿酒酵母中，成熟的GPI锚定蛋白主要含有神经酰胺或二酰基甘油和饱和长脂肪酸，而用于GPI生物合成的传统磷脂酰肌醇（PI）含有不饱和脂肪酸。本文中，我们报道了酿酒酵母Cwh43p，其n端区域包含一个与哺乳动物PGAP2同源的序列，参与了GPI锚点脂质部分向神经酰胺的重塑。在cwh43干扰细胞中，gpi锚定蛋白的PI部分含有饱和长脂肪酸和溶酶PI，但不含肌醇磷酸化神经酰胺，后者是野生型细胞中gpi锚定蛋白的主要脂质部分。此外，Cwh43p的c端区域（Cwh43-C）在PGAP2中不存在，对于将GPI脂质重塑为神经酰胺的能力至关重要。Cwh43p的n端区域（Cwh43-N）与Cwh43-C相关联，促进了Cwh43-C对神经酰胺的脂质重塑。我们的研究结果还表明，分别与Cwh43-N和cwh43 -C同源的小鼠FRAG1和C130090K23也具有这些活性。
The glycosylphosphatidylinositol (GPI)-anchored proteins are subjected to lipid remodeling during their biosynthesis. In the yeast Saccharomyces cerevisiae, the mature GPI-anchored proteins contain mainly ceramide or diacylglycerol with a saturated long-fatty acid, whereas conventional phosphatidylinositol (PI) used for GPI biosynthesis contains an unsaturated fatty acid. Here, we report that S. cerevisiae Cwh43p, whose N-terminal region contains a sequence homologous to mammalian PGAP2, is involved in the remodeling of the lipid moiety of GPI anchors to ceramides. In cwh43 disruptant cells, the PI moiety of the GPI-anchored protein contains a saturated long fatty acid and lyso-PI but not inositolphosphorylceramides, which are the main lipid moieties of GPI-anchored proteins from wild-type cells. Moreover, the C-terminal region of Cwh43p (Cwh43-C), which is not present in PGAP2, is essential for the ability to remodel GPI lipids to ceramides. The N-terminal region of Cwh43p (Cwh43-N) is associated with Cwh43-C, and it enhanced the lipid remodeling to ceramides by Cwh43-C. Our results also indicate that mouse FRAG1 and C130090K23, which are homologous to Cwh43-N and -C, respectively, share these activities.