Characterization of the enzymes of the Kennedy pathway for PE formation in Trypanosoma brucei. (360G-Wellcome-078376_B_05_Z)

Trypanosoma brucei is the causative agent of African sleeping sickness, a vector-borne parasitic disease that threatens millions of people in sub-Saharan Africa. Ethanolamine (tN) is a major component of the trypanosome membrane phospholipids, in the form of phosphatidylethanolamine (PE). PE constitutes 25-30% of the total membrane phospholipid of T. brucei and for this reason it has a very important role in maintaining membrane homeostasis; because membrane phospholipids determine membrane fluidity and the surface charge of cell surfaces, ethanolamine utilization and PE biosynthesis are likely to control a variety of cellular processes. In addition, EtN is found as an integral component of the glycosylphosphatidylinositol (GPI) anchor that is required for membrane attachment of cell surface proteins, most notably the Variant Surface Glycoproteins (VSG), which in the bloodstream form of the parasite plays the essential role of protecting the parasite from the host's immune system. Consequently, a trypanosome which can no longer synthesize or replace its surface glycoprotein coat would be cleared by the immune system and accordingly, the biosynthesis of the conserved GPI-anchor has previously been genetically and biochemically validated as a drug target in bloodstream form T. brucei. The analysis of how ethanolamine is metabolized in T. brucei could unravel novel targets for the development of chemotherapeutic drugs, as well as novel insights on how eukaryotes assemble glycolipid components of membranes and membrane-bound proteins at the cell surface.