Monensin prevents terminal glycosylation of the N- and O-linked oligosaccharides of the HLA-DR-associated invariant chain and inhibits its dissociation from the alpha-beta chain complex.
In B-lymphoblastoid cells, the HLA-DR-associated invariant chain is processed to a form containing O-linked as well as N-linked oligosaccharides. After neuraminidase treatment, the O-linked carbohydrate is susceptible to digestion with an endoglycosidase (endo-beta-N-acetylgalactosaminidase) that cleaves glycans with the structure Gal(beta 1----3)-GalNAc-Ser/Thr, and sialic acid can be added back to this core oligosaccharide by specific sialyltransferases. Treatment of cells with the sodium ionophore monensin markedly affects the post-translational processing of the invariant chain, although that of associated alpha and beta chains is minimally affected. Only a small portion of the N-linked carbohydrate on the invariant chain is processed to an endoglycosidase-H-resistant form. The sialic acid residues normally found on the O-linked glycans are not added, but at least the first residue, GalNAc, is added. In addition to the changes in glycosylation, an intracellular accumulation of HLA-DR antigens also occurs in monensin-treated cells. The accumulation of HLA-DR antigens and the overall slower turnover rates of the alpha, beta, and invariant polypeptides observed after monensin treatment probably reflects the build-up of newly synthesized proteins in Golgi apparatus-derived vacuoles coupled with a decrease in normal degradation in lysosomes.
D001402:B-Lymphocytes / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D005663:Furans / Q000494:pharmacology*; D006684:HLA-DR Antigens; D006596:Hexosaminidases; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D046911:Macromolecular Substances; D008985:Monensin / Q000494:pharmacology*; D009439:Neuraminidase; D009844:Oligosaccharides / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011863:Radioimmunoassay; D048809:alpha-N-Acetylgalactosaminidase
D005663:Furans; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D009844:Oligosaccharides; D008985:Monensin; D006596:Hexosaminidases; D009439:Neuraminidase; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase