Protein Synthesis and Degradation
Asialoglycoprotein receptor 1 is a novel PCSK9-independent ligand of liver LDLR cleaved by furin
The hepatic carbohydrate-recognizing asialoglycoprotein receptor (ASGR1) mediates the endocytosis/lysosomal degradation of desialylated glycoproteins following binding to terminal galactose/N-acetylgalactosamine. Human heterozygote carriers of ASGR1 deletions exhibit ∼34% lower risk of coronary artery disease and ∼10% to 14% reduction of non-HDL cholesterol. Since the proprotein convertase PCSK9 is a major degrader of the low-density lipoprotein receptor (LDLR), we investigated the degradation and functionality of LDLR and/or PCSK9 by endogenous/overexpressed ASGR1 using Western blot and immunofluorescence in HepG2-naïve and HepG2-PCSK9-knockout cells.Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other
Background It was reported that amyloid precursor-like protein 2 (APLP2) increases PCSK9-mediated low-density lipoprotein receptor (LDLR) degradation, and sortilin facilitates PCSK9 secretion. Results APLP2 or sortilin deficiency/overexpression in cells/mice did not affect LDLR degradation by PCSK9. However, APLP2 binds sortilin, and PCSK9 enhances their degradation. Conclusion APLP2/sortilin are not required for PCSK9 activity on LDLR, but their interaction may modulate APLP2 functions. Significance APLP2 and sortilin do not affect LDLR levels.
