Structural Control of Sugar Chains in Animal Cells

Abstract

Sugar chains are synthesized in cells by sequential reactions of glycosylation enzymes. These sugar chains do not have uniform structure, but rather constitute a mixture of various structures which correspond to the intermediates of maturation. Sugar chains on recombinant glycoproteins produced by animal cells also contain various forms. A method of producing uniform glycoproteins with specific sugar chain structure is required. We have been studying biosynthetic control of sugar chains on glycoproteins using animal cells. In the present review, we present the results of our research, focusing on the following two subjects: remodeling branch structures of complex-type sugar chains on interferon-γ (IFN-γ); control of addition of bisecting GlcNAc to immunoglobulin M (IgM). In the investigation into sugar chains on IFN-γ, we used Chinese hamster ovary cells as hosts for recombinant production of IFN-γ, and overexpressed genes for N-acetylglucosaminyltransferases IV and V, thereby changing sugar chains on IFN-γ to highly branched types. In the investigation into sugar chains on IgM, we controlled addition of bisecting GlcNAc to sugar chains on IgM by regulating intracellular activity of β1,4-galactosyltransferase and N-acetylglucosaminyltransferase III. Our results show that regulation of the expression of glycosylation enzymes can be effectively used to control sugar chain structures.