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Nat Commun. 2020 Feb 13;11(1):860. doi: 10.1038/s41467-020-14678-2.

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

Author information

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.
4
Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University, 1-1 Yanagido, Gifu-City, Gifu 501-1193, Japan.
5
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan. tkinoshi@biken.osaka-u.ac.jp.
6
WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan. tkinoshi@biken.osaka-u.ac.jp.

Abstract

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.

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