The regulation of neural-specific glycosylation in Drosophila melanogaster

Abstract

The addition of carbohydrate structures (glycans) to proteins is an essential post-translational modification that begins in the endoplasmic reticulum and is completed through Golgi remodeling. Glycosylation can be cell-specific, tissue-specific, and developmental stage-specific. Altered glycosylation patterns are a hallmark of many cancers as well as many neuronal and muscular diseases, and developmental disorders. However, the mechanisms that regulate glycosylation in a tissue-specific manner are not well understood. A genetic screen in Drosophila melanogaster yielded a mutation called sugar-free frosting (sff), the Drosophila homolog of SAD kinase. Analysis of all of the N-linked glycans in sff mutant embryos revealed a shift towards more complex structures, a shift determined to stem from altered Golgi compartmentation. Many signaling pathways impinge on sff/SAD function, allowing the cellular microenvironment to exert minute control over the N-glycosylation patterns of neurons. One of those pathways receives signaling from a Toll-like receptor (Tollo) expressed on a neighboring non-neural cell. Pharmacological studies indicate that the signal relayed to the neural cell is a biogenic amine. In addition, White, which contributes to eye pigment biosynthesis, interacts with Sff/SAD and influences the phenotypes associated with the sff mutation. White also influences N-glycan expression. Therefore, White, biogenic amines, and Sugar-free frosting/SAD kinase, define nodes in a pathway that modulates neural-specific glycosylation in Drosophila.