Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation.,Nature Communications

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Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation.
Nature Communications ( IF 14.7 ) Pub Date : 2020-02-13 , DOI: 10.1038/s41467-020-14678-2
Yicheng Wang _{1,

2} , Yusuke Maeda ₁ , Yi-Shi Liu ₃ , Yoko Takada ₂ , Akinori Ninomiya ₁ , Tetsuya Hirata _{1,

2,

4} , Morihisa Fujita ₃ , Yoshiko Murakami _{1,

2} , Taroh Kinoshita _{1,

2}

Affiliation

Glycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids interact with each other in the mammalian plasma membranes, forming dynamic microdomains. How their interaction starts in the cells has been unclear. Here, based on a genome-wide CRISPR-Cas9 genetic screen for genes required for GPI side-chain modification by galactose in the Golgi apparatus, we report that β1,3-galactosyltransferase 4 (B3GALT4), the previously characterized GM1 ganglioside synthase, additionally functions in transferring galactose to the N-acetylgalactosamine side-chain of GPI. Furthermore, B3GALT4 requires lactosylceramide for the efficient GPI side-chain galactosylation. Thus, our work demonstrates previously unexpected functional relationships between GPI-anchored proteins and glycosphingolipids in the Golgi. Through the same screening, we also show that GPI biosynthesis in the endoplasmic reticulum (ER) is severely suppressed by ER-associated degradation to prevent GPI accumulation when the transfer of synthesized GPI to proteins is defective. Our data demonstrates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system.

中文翻译：

糖基磷脂酰肌醇生物合成与糖鞘脂生物合成和ER相关降解的串扰。

糖基磷脂酰肌醇（GPI）锚定的蛋白质和糖鞘脂在哺乳动物的质膜中相互作用，形成动态的微区。它们在细胞中的相互作用如何开始尚不清楚。在这里，基于高尔基体中半乳糖修饰GPI侧链所需的基因的全基因组CRISPR-Cas9遗传筛选，我们报道了以前表征为GM1神经节苷脂合酶的β1,3-半乳糖基转移酶4（B3GALT4）。在将半乳糖转移至GPI的N-乙酰半乳糖胺侧链中发挥功能。此外，B3GALT4需要乳糖基神经酰胺才能有效进行GPI侧链半乳糖基化。因此，我们的工作证明了高尔基体中GPI锚定的蛋白与糖鞘脂之间的出乎意料的功能关系。通过相同的筛选我们还表明内质网（ER）中的GPI生物合成受到ER相关降解的严重抑制，从而在合成GPI向蛋白质的转移有缺陷时防止GPI积累。我们的数据证明了GPI生物合成与糖鞘脂生物合成和ER质量控制系统之间的相互影响。

更新日期：2020-02-13

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