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A more recent version of this article appeared on March 1, 2003
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Submitted on March 27, 2002
Revised on October 22, 2002
Accepted on November 6, 2002
1 Wellcome Centre for Molecular Parasitology, University of Glasgow, The Anderson College, Glasgow G11 6NU, UK
2 Wellcome Trust Laboratories for Molecular Parasitology, Department of Biological Sciences and Centre for Molecular Microbiology and Infection, Imperial College, London SW7 2AY, UK
3 Wellcome Centre for Molecular Parasitology, University of Glasgow, The Anderson College, 56 Dumbarton Rd, Glasgow G11 6NU, Scotland, UK
* Corresponding author. E-mail address: j.mottram{at}udcf.gla.ac.uk.
The survival of Trypanosoma brucei, the causative agent of Sleeping Sickness and Nagana, is facilitated by the expression of a dense surface coat of glycosylphosphatidylinositol (GPI)-anchored proteins in both its mammalian and tsetse fly hosts. We have characterised T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds pre-formed GPI anchors onto nascent polypeptides. Deletion of GPI8 (to give 
gpi8) resulted in the absence of GPI-anchored proteins from the cell surface of procyclic form trypanosomes and accumulation of a pool of non-protein-linked GPI molecules, some of which are surface located. Procyclic gpi8, while viable in culture, were unable to establish infections in the tsetse mid-gut, confirming that GPI-anchored proteins are essential for insect-parasite interactions. Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of non-anchored variant surface glycoprotein and cell death with a defined multi-nuclear, multi-kinetoplast and multi-flagellar phenotype indicative of a block in cytokinesis. These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression.
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