Regulation of glycoprotein biosynthesis by formation of specific glycosyltransferase complexes.

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Abstract
Eukaryotic cell surfaces simultaneously express a complex array of protein-linked oligosaccharides and, during differentiation and on neoplastic transformation, these arrays change. The oligosaccharides linked to asparagine residues of proteins are a complex family of structures that are derived from a common precursor oligosaccharide by a network of competing biosynthetic pathways. The glycosylation reactions that make up these biosynthetic pathways often share common intermediates, requiring the competition between rival glycosyltransferases to be regulated at the supramolecular level. Investigation of 2 sequential glycosyltransferases [from porcine liver] that together add N-acetyllactosamine to glycoproteins has revealed their ability to form specific complexes. The functional consequences of complex formation were assessed by investigating the coupled reaction carried out by these sequential enzymes. The membrane enzymes are readily adsorbed by preformed liposomes, and their ability to interact after liposome adsorption has allowed direct investigation of the role played by complex formation. Comparison of the coupled reaction carried out by these sequential enzymes when they are coadsorbed to the same liposome or adsorbed to separate liposomes shows the preferential use of endogenously generated intermediate over exogenously added glycoproteins. This facilitated passage of the intermediate glycosylated glycoprotein within the complex results in a tight coupling of the sequential enzymes. The formation of such complexes by sequential glycosyltransferases is proposed as a mechanism for controlling the completition between potentially rival glycosylation sequences during glycoprotein synthesis. The formation of different specific complexes under different conditions provides a flexible mechanism for regulating the synthesis of cell surface glycoproteins during development.