Will the transgenic mouse serve as a Rosetta Stone to glycoconjugate function?
The overwhelming diversity of oligosaccharide structures on glycoproteins and glycolipids is both the most fascinating and the most frustrating aspect of glycobiology. Moreover, a single protein may be variably glycosylated and thereby represented by multiple glycoforms. As envisioned, many modifications may serve no useful function while others are likely to be essential [1]; hence, experimental approaches to understand the biological basis for such complexity can be difficult to formulate. In a recent comprehensive review on oligosaccharide function [2], Varki concludes that oligosaccharides carry out a large number of biological roles and that 'while all theories are correct, exceptions to each can be found'. Although a common theme to oligosaccharide function may never appear, crucial biological information can be observed to reside within various glycoforms. Examples include the glycoform-dependent mechanism of selectin function in mediating haemopoietic cell extravasation during inflammatory responses [3] and the clearance of particular glycoforms from serum by various glycoform-specific receptors [4-6]. Together, studies of glycosyltransferase biochemistry, naturally-occurring and experimentally-induced glycoform mutations, and the genetic basis for the production of glycoform complexity have allowed crucial steps in the biosynthesis of specific glycan structures to be reconstructed as they appear to occur in the endoplasmic reticulum and Golgi apparatus of intact cells [7]. With a significant foundation of biochemical knowledge achieved, genetic approaches are under way further to decipher the physiological roles encoded within the diverse and dynamic mammalian oligosaccharide repertoire.
Marth
J D
JD
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
D000818:Animals; D006001:Glycoconjugates / Q000235:genetics*; D016695:Glycosyltransferases / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic
D006001:Glycoconjugates; D016695:Glycosyltransferases