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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / deficiency
  • Acyltransferases / genetics
  • Acyltransferases / metabolism
  • CRISPR-Cas Systems
  • Endoplasmic Reticulum-Associated Degradation* / genetics
  • Galactosyltransferases / deficiency
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism
  • Gene Knockout Techniques
  • Glycosphingolipids / biosynthesis*
  • Glycosphingolipids / genetics
  • Glycosylphosphatidylinositols / biosynthesis*
  • Glycosylphosphatidylinositols / genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Glycosphingolipids
  • Glycosylphosphatidylinositols
  • Recombinant Fusion Proteins
  • Acyltransferases
  • COOH-terminal signal transamidase
  • Galactosyltransferases
  • UDP-Gal-betaGlcNAc beta 1,3-galactosyltransferase, human