Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis

J. Engel, P.S. Schmalhorst, A. Kruger, C. Muller, F. Buettner, F. Routier, Glycobiology 25 (2015) 1423–1430.

Download
No fulltext has been uploaded. References only!

Journal Article | Published | English
Author
; ; ; ; ;
Department
Abstract
Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man) linked at position 2 of the inositol. However, several pathogenic fungi additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC synthesized by this fungus. In this study, we identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC; a phenotype that could be reverted by episomal expression of GntA in the mutant. The N-acetylhexosaminyltransferase activity of GntA was substantiated by production of N-acetylhexosamine-IPC in the yeast Saccharomyces cerevisiae upon GntA expression. Using an in vitro assay, GntA was furthermore shown to use UDP-N-acetylglucosamine as donor substrate to generate a glycolipid product resistant to saponification and to digestion by phosphatidylinositol-phospholipase C as expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis.
Publishing Year
Date Published
2015-12-01
Journal Title
Glycobiology
Volume
25
Issue
12
Page
1423 - 1430
IST-REx-ID

Cite this

Engel J, Schmalhorst PS, Kruger A, Muller C, Buettner F, Routier F. Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. Glycobiology. 2015;25(12):1423-1430. doi:10.1093/glycob/cwv059
Engel, J., Schmalhorst, P. S., Kruger, A., Muller, C., Buettner, F., & Routier, F. (2015). Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. Glycobiology, 25(12), 1423–1430. https://doi.org/10.1093/glycob/cwv059
Engel, Jakob, Philipp S Schmalhorst, Anke Kruger, Christina Muller, Falk Buettner, and Françoise Routier. “Characterization of an N-Acetylglucosaminyltransferase Involved in Aspergillus Fumigatus Zwitterionic Glycoinositolphosphoceramide Biosynthesis.” Glycobiology 25, no. 12 (2015): 1423–30. https://doi.org/10.1093/glycob/cwv059.
J. Engel, P. S. Schmalhorst, A. Kruger, C. Muller, F. Buettner, and F. Routier, “Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis,” Glycobiology, vol. 25, no. 12, pp. 1423–1430, 2015.
Engel J, Schmalhorst PS, Kruger A, Muller C, Buettner F, Routier F. 2015. Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis. Glycobiology. 25(12), 1423–1430.
Engel, Jakob, et al. “Characterization of an N-Acetylglucosaminyltransferase Involved in Aspergillus Fumigatus Zwitterionic Glycoinositolphosphoceramide Biosynthesis.” Glycobiology, vol. 25, no. 12, Oxford University Press, 2015, pp. 1423–30, doi:10.1093/glycob/cwv059.

Export

Marked Publications

Open Data IST Research Explorer

Sources

PMID: 26306635
PubMed | Europe PMC

Search this title in

Google Scholar