Cross-Talks of Glycosylphosphatidylinositol Biosynthesis with Glycosphingolipid Biosynthesis and ER-Associated Degradation
ARTICLE https://doi.org/10.1038/s41467-020-14678-2 OPEN Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation Yicheng Wang 1,2, Yusuke Maeda 1, Yi-Shi Liu3, Yoko Takada 2, Akinori Ninomiya 1, Tetsuya Hirata1,2,4, ✉ Morihisa Fujita3, Yoshiko Murakami 1,2 & Taroh Kinoshita 1,2 1234567890():,; 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 char- acterized 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 unex- pected 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 accu- mulation when the transfer of synthesized GPI to proteins is defective. Our data demon- strates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system. 1 Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. 2 WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. 3 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, China.
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