Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes
Version of Record online: 4 APR 2014
© 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
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Special Issue: Malaria
Volume 16, Issue 5, pages 709–733, May 2014
How to Cite
Wirth, C. C., Glushakova, S., Scheuermayer, M., Repnik, U., Garg, S., Schaack, D., Kachman, M. M., Weißbach, T., Zimmerberg, J., Dandekar, T., Griffiths, G., Chitnis, C. E., Singh, S., Fischer, R. and Pradel, G. (2014), Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes. Cellular Microbiology, 16: 709–733. doi: 10.1111/cmi.12288
- Issue online: 15 APR 2014
- Version of Record online: 4 APR 2014
- Accepted manuscript online: 7 MAR 2014 05:26AM EST
- Manuscript Accepted: 21 FEB 2014
- Manuscript Revised: 17 FEB 2014
- Manuscript Received: 19 DEC 2013
- Deutsche Forschungsgemeinschaft
Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(−)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(−) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(−) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(−) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(−) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(−) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.