The obligate intracellular parasite Plasmodium falciparum causes the most severe forms of human malaria. Apical rhoptry organelles of invasive merozoites contain proteins that are instrumental to the intraerythrocytic development of the parasite. Our group has determined that the RhopHl protein of the high molecular mass rhoptry complex (RhopH) is encoded by genes of the highly-conserved clag (cytoadherence-linked asexual gene) family. In this study, the characterisation of the RhopH 1/Clag proteins is continued. It was ascertained that the family has five members in P. falciparum 3D7 (clag2, -3.1, -3.2, -£and -9), each of which is transcribed. Specific antibodies were raised to demonstrate that all Clags are expressed at the apical end of merozoites, but in an apparently differential distribution. Both Clag3.1 and Clag9 are found in the basal bulb of the rhoptries as part of the RhopH complex. However, Clag2, -3.2 and -8 appear to remain outside the complex and their distribution is distinctly more apical, potentially in the region of the rhoptry neck. It was determined that RhopH complexes contain only individual Clag members in a mutually exclusive association, thereby suggesting the existence of multiple complexes in which specificity is conferred by RhopH 1/Clag. Those Clag proteins that are part of the RhopH complex are carried into the newly invaded red blood cell where they persist. There is evidence to suggest that Clag3.1 and Clag9 are trafficked across the parasitophorous vacuolar membrane, and that their function is in the developing parasite. Clag9 is the most diverse member of the family and was originally proposed to be involved in the pathogenic process of cytoadhesion from the surface of the infected red blood cell. However, we have now identified it as a rhoptry protein. This may suggest that Clag9 is indirectly involved in cytoadherence within the cycle that follows erythrocyte invasion.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:719050 |
| Date | January 2007 |
| Creators | Yim Lim, Brian Youn Sen |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1446012/ |
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