Reversible defects in O-linked glycosylation and LDL receptor expression in a UDP-Gal UDP-GalNAc 4-epimerase deficient mutant

@article{Kingsley1986ReversibleDI,
  title={Reversible defects in O-linked glycosylation and LDL receptor expression in a 
 
 
 UDP-Gal
 
 
 UDP-GalNAc
 
 
 4-epimerase deficient mutant},
  author={David M. Kingsley and Karen F. Kozarsky and Lawrence Hobble and Monty Krieger},
  journal={Cell},
  year={1986},
  volume={44},
  pages={749-759}
}

Three types of low density lipoprotein receptor-deficient mutant have pleiotropic defects in the synthesis of N-linked, O-linked, and lipid- linked carbohydrate chains

Comparisons between the ldl mutants and a large number of previously isolated CHO glycosylation defective mutants showed that the genetic defects in ldlB, ldlC, and ldlD cells were unique and that only very specific types of carbohydrate alteration could dramatically affect LDL receptor function.

Defects in Galactose Metabolism and Glycoconjugate Biosynthesis in a UDP-Glucose Pyrophosphorylase-Deficient Cell Line Are Reversed by Adding Galactose to the Growth Medium

Although the mechanism behind UDP-Glc/Gal production in the UGP-deficient cells remains to be determined, the capacity of this cell line to change its glycosylation status as a function of extracellular Gal1P makes it a useful, reversible model with which to study different aspects of galactose metabolism and glycoconjugate biosynthesis.

Abnormal intracellular sorting of O-linked carbohydrate-deficient interleukin-2 receptors

The abnormal sorting of the Od IL-2 receptor is compared with the O-glycosylation dependence of the surface expression and stability of the low-density lipoprotein receptor, decay-accelerating factor, and the major antigen envelope protein of Epstein-Barr virus.

Defectively N-glycosylated and non-O-glycosylated aminopeptidase N (CD13) is normally expressed at the cell surface and has full enzymatic activity.

It is demonstrated that aminopeptidase N carries "mucin-type" O-glycans and that this is predominantly located in the stalk, which connects the catalytic headgroup to the membrane anchor, in the plasma membrane of the ldl(D) cells.

Mediators of Galactose Sensitivity in UDP-Galactose 4′-Epimerase-impaired Mammalian Cells*

Although GALE activity toward both substrates was required to restore metabolic balance, UDP-GalNAc activity was not required for cell proliferation in the presence of otherwise cytostatic concentrations of galactose, and uridine supplementation enabled ldlD cells to proliferate in the Presence of Gal-1-P and UDP- Gal, these data offer important insights into the mechanism of Galactose sensitivity in epimerase-impaired cells.

Glycosylation mutations of serine/threonine-linked oligosaccharides in low-density lipoprotein receptor: indispensable roles of O-glycosylation.

The low-density lipoprotein (LDL) receptor is a surface glycoprotein that mediates the cellular uptake of LDL, a cholesterol-carrying plasma protein that regulates de novo cholesterol biosynthesis and LDL receptor expression.

Human UDP-galactose 4′-epimerase (GALE) is required for cell-surface glycome structure and function

A role of GALE-mediated NS regulation in death receptor signaling is revealed and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.

UDP-Galactose 4′-Epimerase Activities toward UDP-Gal and UDP-GalNAc Play Different Roles in the Development of Drosophila melanogaster

The results demonstrate that both UDP-gal and UDP-GalNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge.

HEK293T cell lines defective for O-linked glycosylation

Derby derivatives of the HEK293T cell line that are defective in their ability to generate mucin-type O-linked glycosylation are described and will likely prove useful for a wide variety of applications.
...

References

SHOWING 1-10 OF 41 REFERENCES

Three types of low density lipoprotein receptor-deficient mutant have pleiotropic defects in the synthesis of N-linked, O-linked, and lipid- linked carbohydrate chains

Comparisons between the ldl mutants and a large number of previously isolated CHO glycosylation defective mutants showed that the genetic defects in ldlB, ldlC, and ldlD cells were unique and that only very specific types of carbohydrate alteration could dramatically affect LDL receptor function.

Addition of a mannose-6-phosphate-containing oligosaccharide alters cellular processing of low density lipoprotein by parental and LDL-receptor-defective Chinese hamster ovary cells.

The potential use of M56P-LDL in the isolation of cells with pleiotropic mutations affecting receptor-mediated endocytosis is discussed, suggesting differences in the intracellular processing of mannose 6-phosphate-bearing ligands and LDL.

Unusual forms of low density lipoprotein receptors in hamster cell mutants with defects in the receptor structural gene

The finding of multiple mutant forms of the LDL receptor in ldlA mutants, some of which appeared together in the same cell, confirm that the ldnA locus is the structural gene for the LDL receptors.

Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity.

  • D. KingsleyM. Krieger
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1984
Results suggest that the ldlA locus is the structural gene for the LDL receptor in CHO cells, which must have defects in genes that are required for either the regulation, synthesis, transport, recycling, or turnover of LDL receptors.

Deletion of clustered O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibroblasts.

It is concluded that: 1) the serine- and threonine-rich region of the LDL receptor is the site for addition of clustered O-linked carbohydrates; 2) the receptor contains a small number of isolated chains of O- linked carbohydrates in addition to the clustered chains; and 3) the clustered O -linked carbohydrates are not essential for LDL receptor function in cultured hamster fibroblasts.

The metabolism of d-galactosamine and N-acetyl-d-galactosamine in rat liver.

Analysis of the [1-(14)C]glucosamine-containing disaccharides released from glycogen by beta-amylase provided additional evidence that they consist of a mixture of glucose and glucosamine in a 1:1 ratio, but with glucose predominating on the reducing end.