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Papers In Press, published online ahead of print March 1, 2004
J. Lipid Res., doi:10.1194/jlr.R300020-JLR200
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Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912
Corresponding Author: ryu{at}mcg.edu
Ganglioside biosynthesis is strictly regulated by the activities of glycosyltransferases and is necessarily controlled at the levels of gene transcription and post-translational modification. Cells can switch between expressing simple and complex gangliosides, or between different series within these two groups. The sequential biosynthesis of gangliosides in parallel enzymatic pathways, however, requires fine-tuned subcellular sequestration and orchestration of glycosyltransferases. A popular model predicts that this regulation is achieved by the vectorial organization of ganglioside biosynthesis: sequential biosynthetic steps occur with traffic of ganglioside intermediates through subsequent subcellular compartments. It is still a matter of ongoing controversy, however, regarding where and how glycosyltransferases are distributed to ensure the vectorial organization of ganglioside biosynthesis. Additionally, it is not clearly understood how the distribution is regulated. Most recent studies show that the co-localization of two glycosyltransferases may result in the formation of enzyme complexes and activation of a particular biosynthetic pathway. Here, we will review current models for the subcellular distribution of glycosyltransferases and discuss results that suggest a critical role of N-glycosylation for processing, transport and complex formation of these enzymes. In this context we will attempt to illustrate the regulation of ganglioside biosynthesis as well as the biological significance of N-glycosylation as a post-translational regulatory mechanism. We will review the results of analyses of the 5’-regulatory sequences of several glycosyltransferases in ganglioside biosynthesis, and provide insights into how their synthesis can be regulated at the level of transcription.
Revised on February 23, 2004
Accepted on February 24, 2004
Regulation of ganglioside biosynthesis in the nervous system
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