Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation.
Acyltransferases
/ deficiency
CRISPR-Cas Systems
Endoplasmic Reticulum-Associated Degradation
/ genetics
Galactosyltransferases
/ deficiency
Gene Knockout Techniques
Glycosphingolipids
/ biosynthesis
Glycosylphosphatidylinositols
/ biosynthesis
HEK293 Cells
HeLa Cells
Humans
Models, Molecular
Recombinant Fusion Proteins
/ chemistry
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 02 2020
13 02 2020
Historique:
received:
25
08
2019
accepted:
27
01
2020
entrez:
15
2
2020
pubmed:
15
2
2020
medline:
28
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32054864
doi: 10.1038/s41467-020-14678-2
pii: 10.1038/s41467-020-14678-2
pmc: PMC7018848
doi:
Substances chimiques
Glycosphingolipids
0
Glycosylphosphatidylinositols
0
Recombinant Fusion Proteins
0
Acyltransferases
EC 2.3.-
COOH-terminal signal transamidase
EC 2.3.2.-
Galactosyltransferases
EC 2.4.1.-
UDP-Gal-betaGlcNAc beta 1,3-galactosyltransferase, human
EC 2.4.1.62
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
860Références
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