Effect of inhibitors of N-linked oligosaccharide processing on the cell surface expression of a melanoma integrin.
The role of trimming and processing of N-linked oligosaccharides on the cell surface expression of the melanoma vitronectin receptor, a member of the integrin family of cell adhesion receptors, was examined by using specific glucosidase and mannosidase inhibitors. Inhibition of glucosidases I and II by castanospermine or N-methyldeoxynojirimycin delayed the vitronectin receptor alpha/beta chain heterodimer assembly and alpha chain cleavage and resulted in a decrease in the level of expression cell surface receptor. Conversely, the vitronectin receptor synthesized in the presence of the mannosidase I and II inhibitors, 1-deoxymannojirimycin and swainsonine, was transported normally to the cell surface with its alpha chain N-linked oligosaccharides in an endoglycosidase H-sensitive form. In the presence of swainsonine, time course studies of the cell surface replacement of control, endoglycosidase H-resistant receptor with an endoglycosidase H-sensitive form demonstrated a vitronectin receptor half-life of approximately 15-16 h. These studies provide evidence that the rates of assembly, proteolytic cleavage, and cell surface expression of the melanoma vitronectin receptor are dependent on the initial trimming of glucosyl residues from the alpha chain N-linked oligosaccharides.
Spiro
R C
RC
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Laufer
D M
DM
Perry
S K
SK
Harper
J R
JR
D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005959:Glucosidases / Q000502:physiology*; D006801:Humans; D008361:Mannosidases / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D011971:Receptors, Immunologic; D019030:Receptors, Vitronectin; D005959:Glucosidases; D008361:Mannosidases