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The clinical symptoms of the parasitic disease malaria are caused by the intraerythrocytic stage of the Plasmodium spp life cycle. The invasive form of the malarial parasite for erythrocytes is the merozoite. Erythrocyte invasion is a multistep process and proteins required for this event are transcribed during the schizont stage and subsequently expressed at the merozoite stage. The merozoite is able to invade erythrocytes using a wide range of invasion pathways. Invasion pathways are determined by erythrocyte and merozoite properties. Erythrocyte characteristics and availability of erythrocyte receptors are crucial criteria for successful invasion. Each parasite clone possesses unique invasion properties: firstly the parasite clone does not necessarily express all homologues of the invasion protein family; secondly, the amount of a particular protein being expressed may vary; and thirdly some proteins are predominantly expressed over others. The Plasmodium falciparum clone W2mef is able to switch from a sialic aciddependent to independent (W2mef/NM) invasion pathway when selected in the presence of neuraminidase-treated erythrocytes. Neuraminidase cleaves sialic acid from erythrocyte surface proteins thus limiting the availability of erythrocyte receptors. Some aspects of the molecular mechanism underlying this switch has been determined by Stubbs et al., (2005) and Gaur et al., (2006) by transcriptional assessment of the schizont stage and subsequent expression analysis of identified candidate molecules. Recent studies have though shown that invasion molecules may not only be regulated at the transcriptional stage, but also during protein expression. By using a novel ̂ quantitative proteomic approach (iTRAQ) this present study investigates merozoite protein expression profiles and reveals differences in protein expression between W2mef and W2mef/NM. Of the 600 proteins that were quantitatively analysed 88 proteins show differential expression in W2mef/NM versus W2mef. Furthermore, this study exploits the ability of the W2mef clone to switch between invasion pathways as a tool to uncover the gene regulation mechanism by directly comparing gene transcription during the schizont stage and protein expression at the merozoite stage. Post-transcriptional regulation appears to i ATTENTION: The Singapore Copyright Act applies to the use of this document. Nanyang Technological University Library

Invasion pathway switching of plasmodium falciparum reveals post-transcriptional regulation of merozoite proteins