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O-glycosylation enzymes: Directing traffic during Drosophila embryogenesis

Copyright © 2006 ASBMB

O-glycosylation is an abundant posttranslational modification of mucins, extracellular surface proteins found on epithelial cells in all higher organisms. The O-glycosylation of mucins starts with the attachment of a N-acetylgalactosamine to serine or threonine through the action of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases; this type of glycosylation, typical for mucins and found on other proteins, is called mucin-type O-glycosylation. At least nine polypeptide N-acetylgalactosaminyltransferases (ppGaNTases) are found in Drosophila. The ppGaNTase PGANT35A, has been shown to be essential for the viability of Drosophila embryos and now, in The Journal of Biological Chemistry, Tian and Ten Hagen describe the developmental and cellular defects that are lethal to embryos lacking the wild-type pgant35a gene.

The researchers showed that pgant35A is expressed during Drosophila embryogenesis from stage 15 onwards, when intense apical secretion of proteins takes place in the developing tracheal system. In contrast with wild-type flies, embryos lacking a functional pgant35A gene had a highly irregular tracheal system. Among other cell polarity markers, the level of Crumbs, an apical determinant that localises to the extracellular membrane, was reduced in tracheal cells and was found intracellularly, suggesting that pgant35A deficiency impairs protein trafficking. Dextran dye injected into the mutant embryos diffused into the tracheal tubes, indicating that the barrier function of the epithelial tubes was also disturbed.

Antibody staining revealed that O-glycosylation within the trachea of pgant35A mutants was substantially reduced at stage 17. GalNAcylated structures detected in stage 15 were probably due to pgant2 activity suggesting that the various Drosophila pgant genes are active at different stages of development. N-glycosylation and chitin synthesis were unaffected, suggesting that the alterations of tracheal cells were due to diminished mucin-type O-glycosylation normally initiated by PGANT35A in the wild-type. In other tissues of ectodermal origin, mucin-type O-glycosylation was only slightly reduced, perhaps because the lack of pgant35A activity was compensated by other pgants.

Taken together, Tian and Ten Hagen show for the first time the importance of mucin-type O-glycosylation at a specific stage of Drosophila embryogenesis. They propose that the lack of this glycosylation impairs protein trafficking in epithelial cells, preventing the complete establishment of basoapical cell polarity. As there appears to be less redundancy in the actions of glycosyltransferases in Drosophila, it might turn out to be a more tractable model for studying the role of glycosylation during development than mice.

Author: Mirko von Elstermann