Format

Send to

Choose Destination
Open Biol. 2015 Dec;5(12):150234. doi: 10.1098/rsob.150234.

Dual functionality of O-GlcNAc transferase is required for Drosophila development.

Author information

1
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
2
Division of Molecular Microbiology, University of Dundee, Dundee, UK.
3
Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee, UK.
4
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK Division of Molecular Microbiology, University of Dundee, Dundee, UK dmfvanaalten@dundee.ac.uk.

Abstract

Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity.

KEYWORDS:

Drosophila development; Hox; O-GlcNAc; O-GlcNAc transferase

PMID:
26674417
PMCID:
PMC4703063
DOI:
10.1098/rsob.150234
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center