Artikel
The role of proteases during the egress of malaria gametocytes from the enveloping erythrocyte
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Veröffentlicht: | 8. Januar 2013 |
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Gliederung
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The transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by sexual precursor cells, the intraerythrocytic gametocytes which become activated in the mosquito midgut by environmental stimuli and then undergo gametogenesis. Because gametocytes are the only life-cycle stages of the parasite that are able to establish an infection in the mosquito, they play an important role in spreading the tropical disease. Gametocyte egress from the enveloping erythrocyte is a crucial step for the parasite to prepare for fertilization, but the molecular mechanisms are not well understood. We show that P. falciparum gametocytes exit the erythrocyte by an inside-out type of egress. The parasitophorous vacuole membrane (PVM) ruptures at multiple sites within less than a minute after activation. Following PVM rupture the inner membrane complex begins to disintegrate, while the gametocyte is in the process of round up. At approximately 15 min post-activation, the erythrocyte membrane ruptures with the formation of a pore. We show that erythrocyte rupture can be inhibited by the cysteine/serine protease inhibitors TLCK and TPCK. Inhibitors directed against the cysteine protease dipeptidyl aminopeptidase PfDPAP3, on the other hand, prevent the rupture of the PVM. PfDAP3 was previously shown to activate the subtilisin protease PfSUB1 during egress. It is now our aim to investigate the function of PfSUB1 in gametocyte egress by the use of loss-of-function mutants, which will be generated via a dominant negative expression approach. Identifying the role of proteases will lead to a better understanding of the molecular mechanisms behind gametocyte egress and may point to new targets for transmission blocking strategies.