PT  - JOURNAL ARTICLE
AU  - Yicheng Wang
AU  - Yusuke Maeda
AU  - Yishi Liu
AU  - Yoko Takada
AU  - Akinori Ninomiya
AU  - Tetsuya Hirata
AU  - Morihisa Fujita
AU  - Yoshiko Murakami
AU  - Taroh Kinoshita
TI  - Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation
AID  - 10.1101/743914
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 743914
4099  - http://biorxiv.org/content/early/2019/08/24/743914.short
4100  - http://biorxiv.org/content/early/2019/08/24/743914.full
AB  - 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), also called 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 evolutionary and 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.