Poster Presentation Melbourne Protein Group Student Symposium 2013

Trafficking of virulence proteins in malaria parasite-infected erythrocytes (#53)

Emma McHugh 1 2 3 , Matthew Dixon 1 2 3 , Don Gardiner 4 , Katharine Trenholme 4 , Leann Tilley 1 2 3
  1. Biochemistry and Molecular Biology, The University of Melbourne, Parkville, VIC, Australia
  2. ARC Centre of Excellence for Coherent X-ray Science, The University of Melbourne, Parkville, VIC, Australia
  3. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
  4. Malaria Biology Laboratory, Queensland Institute of Medical Research, Herston, QLD, Australia
The most severe forms of human malaria are caused by Plasmodium falciparum, an apicomplexan parasite that undergoes asexual replication within red blood cells. Infected erythrocytes gain the ability to adhere to endothelial cells in the host microvasculature through a virulence complex on the cell surface. This process, termed cytoadherence, requires P. falciparum to produce and export a range of proteins to the surface of the host erythrocyte which possesses no endogenous protein trafficking apparatus. Membranous parasite-derived structures called Maurer’s clefts that exist in the erythrocyte cytoplasm play a key role in the sorting of proteins involved in cytoadherence. Ring exported protein 1 (REX1) is a Maurer’s cleft protein required for expression of the major virulence protein on the red blood cell surface. The C terminal of REX1 contains a repeat region which varies between parasite strains and diversity of these repeats is thought to be linked to parasite virulence. In order to investigate the role of the C terminal repeat region of REX1 in virulence protein trafficking, we have performed binding assays to characterise the cytoadherence phenotype of several REX1 truncation, replacement and wild type parasites. We have observed altered Maurer’s cleft structure in parasites with deletion of the C terminal repeat region. Trypsin cleavage assays, where the protease trypsin is used to cleave the extracellular portion of the major virulence protein, have been performed to assess differences in virulence protein surface expression.