Protein trafficking mechanisms in the human malarial parasite P. falciparum

• Applicant: Professor Dr. Jude Marek Przyborski
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2006 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 29282676

Having invaded mature human erythrocytes, Plasmodium falciparum the aetiological agent of malaria tropica, exports proteins beyond the boundaries of its own plasma membrane, into the host erythrocyte. Many of these parasite-encoded proteins have been implicated in structural and physiological changes in the infected host cell. Some of these proteins are important factors in the pathology of malaria. The host erythrocyte does not, itself, have the necessary molecular machinery to traffic proteins to their eventual destinations in the host cell. Thus, it appears that the parasite itself exports a functional secretory system into the metabolically ¿dead¿ host cell, an interesting paradigm in cell biology. The unusual nature of the parasites secretory system is further underlined by unusual protein targeting motifs. Thus, it can be shown that many parasite proteins exported into the host erythrocyte do not possess a canonical N¿terminal ER targeting sequence, a pre-requisite for entry into the secretory system. However, many of these proteins do contain a recessed hydrophobic domain towards their N-terminal end. This signal has been suggested to fulfil the function of a secretory signal sequence, however mechanistic data on how this signal mediates ER translocation remain sparse. In this funding period, we shall address the question as to how these hydrophobic domains mediate ER translocation. We have designed experimental strategies to perform an ER translocation assay in order to mechanistically dissect the initial steps in the parasites early secretory pathway. This study may uncover novel ER translocation mechanisms playing a role in ER translocation processes in other cell types. Furthermore, we aim to address how the folding state of proteins affects their trafficking to the cytosol of the host erythrocyte.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1131: Life Inside Cells