Nucleotide-sugar transporters: structure, function and roles in vivo

Abstract

The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotidesugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation. Correspondence

Engineering Mammalian Mucin-type O-Glycosylation in Plants

“…High concentrations of nucleotide sugars in Golgi are maintained by transporters, and it has been suggested that plants lack a specific transporter (43, 44) for UDP-GalNAc (23). Most UDP-Gal transporters, however, function as UDP-Gal/GalNAc transporters (43,(45)(46)(47). We therefore first investigated whether introduction of an epimerase, P. aeruginosa cytoplasmic epimerase (WbpP) (35), and a human GalNAc-T, GalNAc-T2 (48), would be sufficient for O-glycosylation.…”

The Golgi localized bifunctional UDP-rhamnose/UDP-galactose transporter family of Arabidopsis

“…Given the essential roles of NSTs in the glycosylation of proteins, lipids, and proteoglycans, as well as in the biosynthesis of plant cell wall polysaccharides, it is not surprising that these transporters have been identified in all eukaryotes (4). NSTs consist of 300-to 400-aa residues and possess six to 10 transmembrane domains (5,6). Plant NSTs belong to the NST/triose phosphate translocator (TPT) superfamily, and phylogenetic analyses have identified more than 50 members that are distributed in six clades in the reference plant, Arabidopsis thaliana (7) (Fig.…”

Biosynthesis of the Fungal Cell Wall Polysaccharide Galactomannan Requires Intraluminal GDP-mannose

“…Nucleotide sugar transporters form a family of structurally conserved integral membrane proteins that supply the endoplasmic reticulum or Golgi apparatus of eukaryotic cells with donor substrates of glycosyltransferases (18,19). GDP-mannose (GDP-Man) transporters have been studied in various organisms, such as the protozoan parasite Leishmania (20), S. cerevisiae (21), plants (22), and various fungi (23)(24)(25), including two Aspergilli (26,27).…”