Life is sweet! A novel role for N-glycans in Drosophila lifespan

摘要

N-glycans are post-translational modifications in which the sugar chain is covalently linked to protein by a GlcNac beta 1-N-asparagine linkage. Drosophila melanogaster and other invertebrates, but not vertebrates, synthesize large amounts of "paucimannose" N-glycans that contain only three or four mannose residues. The enzyme UDP-GlcNac: alpha 3-D-mannoside beta 1,2-N-acetylglucosaminyltransferase I (GnTI, encoded by the Mgat1 gene) controls the synthesis of paucimannose N-glycans. Either deletion or neuron-specific knockdown of Mgat1 in wild-type flies results in pronounced defects in locomotion, structural defects in the adult central nervous system and a severely reduced lifespan. We have recently shown that neuronal expression of a wild-type Mgat1 transgene in Mgat1-null flies rescues the structural defects in the brain (fused beta-lobes) and the shortened lifespan and, surprisingly, results in a dramatic 135% increase in mean lifespan relative to genetically identical controls that do not express the transgene. In this review, we discuss various approaches that can be used to determine the roles of paucimannose N-glycans in Drosophila longevity and in the adult CNS.