Projects per year
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.
Original language | English |
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Article number | 150234 |
Number of pages | 10 |
Journal | Open Biology |
Volume | 5 |
Issue number | 12 |
DOIs | |
Publication status | Published - 16 Dec 2015 |
Keywords
- O-GlcNAc
- O-GlcNAc transferase
- Drosophila development
- Hox
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Dive into the research topics of 'Dual functionality of O-GlcNAc transferase is required for Drosophila development'. Together they form a unique fingerprint.Projects
- 4 Finished
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Regulation of the Rho GEF Pebble in Fibroblast Growth Factor Dependent Cell Migration
Muller, A. (Investigator)
1/08/13 → 31/07/16
Project: Research
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Strategic Award: Wellcome Trust Technology Platform
Blow, J. (Investigator), Lamond, A. (Investigator) & Owen-Hughes, T. (Investigator)
1/01/13 → 30/09/18
Project: Research
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Dynamics of Fundamental Cellular Processes by Live Cell and Tissue Imaging
MacDonald, M. (Investigator), McGloin, D. (Investigator), McKenna, S. (Investigator), Storey, K. (Investigator), Swedlow, J. (Investigator) & Weijer, K. (Investigator)
1/01/13 → 31/12/17
Project: Research
Profiles
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van Aalten, Daan
- Molecular Cell and Developmental Biology - Professor of Biological Chemistry
Person: Academic