Glycosyltransferase mutants: key to new insights in glycobiology

Abstract

Glycosyltransferases (Glyc-T's) catalyze the synthesis of the carbohydrate portions of glycoproteins, glycolipids, and proteoglycans. Most Glyc-T's transfer one sugar in one linkage and are encoded by a unique gene. Thus, synthesis of a branched carbohydrate may require expression of at least 30 Glyc-T genes. Mutations that alter Glyc-T activity therefore provide an approach to identifying functions for carbohydrates. These fall into two general categories: 1) intramolecular functions pertaining to the physical and biochemical properties of a glycoconjugate; and 2) intermolecular functions that involve recognition of sugar (or sugars) by another molecule, such as the selectins that bind to specific sugar sequences at the cell surface. In this review, the origin, nature, and uses of Glyc-T mutants that have been used to study both types of carbohydrate function will be summarized. Many Glyc-T genes are now cloned, so transgenic and gene disruption techniques are the latest strategies for identifying new functions for carbohydrates. It is already apparent that the consequences of altering the spectrum of carbohydrates expressed by a cell or an organism range from "none" to "death." A key challenge for the future is to identify molecular bases for the complex phenotypes created by glycosylation engineering. Equally important will be to understand factors that regulate Glyc-T genes, a new class of genes whose study may reveal novel mechanisms of biological regulation.