Nuclear receptors FXR and SHP regulate protein N-glycan modifications in the liver.
Sci Adv
; 7(17)2021 04.
Article
in En
| MEDLINE
| ID: mdl-33883138
ABSTRACT
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are key regulators of metabolism. Here, we report a previously unknown function for the hepatic FXR-SHP axis in controlling protein N-linked glycosylation. Transcriptome analysis in liver-specific Fxr-Shp double knockout (LDKO) livers revealed induction of genes encoding enzymes in the N-glycosylation pathway, including Mgat5, Fut8, St3gal6, and St6gal1 FXR activation suppressed Mgat5, while Shp deletion induced St3gal6 and St6gal1 Increased percentages of core-fucosylated and triantennary glycan moieties were seen in LDKO livers, and proteins with the "hyperglycoforms" preferentially localized to exosomes and lysosomes. This up-regulation of N-glycosylation machinery was specific to the Golgi apparatus and not the endoplasmic reticulum. The increased glycan complexity in the LDKO correlated well with dilated unstacked Golgi ribbons and alterations in the secretion of albumin, cholesterol, and triglycerides. Our findings demonstrate a role for the FXR-SHP axis in maintaining glycoprotein diversity in the liver.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Cytoplasmic and Nuclear
/
Liver
Language:
En
Journal:
Sci Adv
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos