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Developmentally regulated sphingolipid synthesis in African trypanosomes.

Authors :
Sutterwala SS
Hsu FF
Sevova ES
Schwartz KJ
Zhang K
Key P
Turk J
Beverley SM
Bangs JD
Source :
Molecular microbiology [Mol Microbiol] 2008 Oct; Vol. 70 (2), pp. 281-96. Date of Electronic Publication: 2008 Aug 11.
Publication Year :
2008

Abstract

Sphingolipids are essential components of eukaryotic membranes, and many unicellular eukaryotes, including kinetoplastid protozoa, are thought to synthesize exclusively inositol phosphorylceramide (IPC). Here we characterize sphingolipids from Trypanosoma brucei, and a trypanosome sphingolipid synthase gene family (TbSLS1-4) that is orthologous to Leishmania IPC synthase. Procyclic trypanosomes contain IPC, but also sphingomyelin, while surprisingly bloodstream-stage parasites contain sphingomyelin and ethanolamine phosphorylceramide (EPC), but no detectable IPC. In vivo fluorescent ceramide labelling confirmed stage-specific biosynthesis of both sphingomyelin and IPC. Expression of TbSLS4 in Leishmania resulted in production of sphingomyelin and EPC suggesting that the TbSLS gene family has bi-functional synthase activity. RNAi silencing of TbSLS1-4 in bloodstream trypanosomes led to rapid growth arrest and eventual cell death. Ceramide levels were increased more than threefold by silencing suggesting a toxic downstream effect mediated by this potent intracellular messenger. Topology predictions support a revised six-transmembrane domain model for the kinetoplastid sphingolipid synthases consistent with the proposed mammalian sphingomyelin synthase structure. This work reveals novel diversity and regulation in sphingolipid metabolism in this important group of human parasites.

Details

Language :
English
ISSN :
1365-2958
Volume :
70
Issue :
2
Database :
MEDLINE
Journal :
Molecular microbiology
Publication Type :
Academic Journal
Accession number :
18699867
Full Text :
https://doi.org/10.1111/j.1365-2958.2008.06393.x