Reductionist animal models to probe protein O-GlcNAcylation
type: CreativeWork
description: Protein O-GlcNAcylation is a reversible type of glycosylation of serine and threonine residues of nucleocytoplasmic proteins occurring in all animals examined to date. Its installation on protein substrates is carried out by O-GlcNAc transferase (OGT), and its removal by O-GlcNAc hydrolase (O-GlcNAcase or OGA). A range of proteomics studies have suggested that over a thousand intracellular proteins are O-GlcNAc modified. However, little is known of the role of O-GlcNAc on these proteins. In a search for a reductionist model with a small proteome to dissect the general global mechanisms of protein O-GlcNAcylation, I discovered the presence of functional OGT, OGA and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant animal, the placozoan Trichoplax adhaerens. I show via enzymatic characterization of Trichoplax OGT/OGA and genetic rescue experiments in Drosophila melanogaster that these proteins possess activities/functions similar to their bilaterian counterparts. While Trichoplax is not currently amenable to genetic manipulation, studying protein O-GlcNAcylation in this organism has revealed the presence of OGT, OGA and O-GlcNAc in non-bilaterian animals. Together with the absence of O-GlcNAcylation in lower organisms, this suggests that OGT-dependent reversible protein O-GlcNAcylation is a metazoan innovation, which may have facilitated the rapid and complex signaling mechanisms required for the evolution of multicellular organisms. Various genetic approaches in several animal models have revealed that protein O-GlcNAcylation is required for embryogenesis. Embryonic development in a genetically tractable organism is thus a model in which the mechanisms of protein O-GlcNAcylation can be investigated. Drosophila melanogaster OGT is a polycomb gene, null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities of the modified proteins involved, and the underlying biology linking these to embryonic de…
abstract: Protein O-GlcNAcylation is a reversible type of glycosylation of serine and threonine residues of nucleocytoplasmic proteins occurring in all animals examined to date. Its installation on protein substrates is carried out by O-GlcNAc transferase (OGT), and its removal by O-GlcNAc hydrolase (O-GlcNAcase or OGA). A range of proteomics studies have suggested that over a thousand intracellular proteins are O-GlcNAc modified. However, little is known of the role of O-GlcNAc on these proteins. In a search for a reductionist model with a small proteome to dissect the general global mechanisms of protein O-GlcNAcylation, I discovered the presence of functional OGT, OGA and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant animal, the placozoan Trichoplax adhaerens. I show via enzymatic characterization of Trichoplax OGT/OGA and genetic rescue experiments in Drosophila melanogaster that these proteins possess activities/functions similar to their bilaterian counterparts. While Trichoplax is not currently amenable to genetic manipulation, studying protein O-GlcNAcylation in this organism has revealed the presence of OGT, OGA and O-GlcNAc in non-bilaterian animals. Together with the absence of O-GlcNAcylation in lower organisms, this suggests that OGT-dependent reversible protein O-GlcNAcylation is a metazoan innovation, which may have facilitated the rapid and complex signaling mechanisms required for the evolution of multicellular organisms. Various genetic approaches in several animal models have revealed that protein O-GlcNAcylation is required for embryogenesis. Embryonic development in a genetically tractable organism is thus a model in which the mechanisms of protein O-GlcNAcylation can be investigated. Drosophila melanogaster OGT is a polycomb gene, null mutants of which display homeotic transformations and die at the pharate adult stage. However, the identities of the modified proteins involved, and the underlying biology linking these to embryonic de…
author: Selvan, Nithya
language: eng
date published: 2015
date modified: 2026-07-24T02:08:12Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee