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Eukaryotic Cell, February 2009, p. 230-240, Vol. 8, No. 2
1535-9778/09/$08.00+0     doi:10.1128/EC.00361-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Trypanosoma brucei UDP-Glucose:Glycoprotein Glucosyltransferase Has Unusual Substrate Specificity and Protects the Parasite from Stress{triangledown} ,§

Luis Izquierdo, Abdel Atrih,{dagger} Joao A. Rodrigues,{ddagger} Deuan C. Jones, and Michael A. J. Ferguson*

Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom

Received 6 November 2008/ Accepted 12 December 2008

In this paper, we describe the range of N-linked glycan structures produced by wild-type and glucosidase II null mutant bloodstream form Trypanosoma brucei parasites and the creation and characterization of a bloodstream form Trypanosoma brucei UDP-glucose:glycoprotein glucosyltransferase null mutant. These analyses highlight peculiarities of the Trypanosoma brucei UDP-glucose:glycoprotein glucosyltransferase, including an unusually wide substrate specificity, ranging from Man5GlcNAc2 to Man9GlcNAc2 glycans, and an unusually high efficiency in vivo, quantitatively glucosylating the Asn263 N-glycan of variant surface glycoprotein (VSG) 221 and 75% of all non-VSG N glycosylation sites. We also show that although Trypanosoma brucei UDP-glucose:glycoprotein glucosyltransferase is not essential for parasite growth at 37°C, it is essential for parasite growth and survival at 40°C. The null mutant was also shown to be hypersensitive to the effects of the N glycosylation inhibitor tunicamycin. Further analysis of bloodstream form Trypanosoma brucei under normal conditions and stress conditions suggests that it does not have a classical unfolded protein response triggered by sensing unfolded proteins in the endoplasmic reticulum. Rather, judging by its uniform Grp78/BiP levels, it appears to have an unregulated and constitutively active endoplasmic reticulum protein folding system. We suggest that the latter may be particularly appropriate for this organism, which has an extremely high flux of glycoproteins through its secretory pathway.

* Corresponding author. Mailing address: MSI/WTB Complex, Dow St., Dundee DD15EH, United Kingdom. Phone: 44-1382-384219. Fax: 44-1382-348896. E-mail: m.a.j.ferguson{at}dundee.ac.uk

{triangledown} Published ahead of print on 29 December 2008.

§ Supplemental material for this article may be found at http://ec.asm.org/.

{dagger} Present address: TMRC laboratories, University of Dundee, Dundee DD1 5EH, United Kingdom.

{ddagger} Present address: Centre for Malaria and Tropical Diseases, Institute of Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal.

Eukaryotic Cell, February 2009, p. 230-240, Vol. 8, No. 2
1535-9778/09/$08.00+0     doi:10.1128/EC.00361-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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