Malaria Parasite Signal Peptide Peptidase is an ER-Resident Protease Required for Growth but not for Invasion
Danushka S Marapana, Danny W Wilson, Elizabeth S Zuccala, Chaitali D Dekiwadia, James G Beeson, Stuart A Ralph, Jake Baum
TRAFFIC | WILEY-BLACKWELL | Published : 2012
The establishment of parasite infection within the human erythrocyte is an essential stage in the development of malaria disease. As such, significant interest has focused on the mechanics that underpin invasion and on characterization of parasite molecules involved. Previous evidence has implicated a presenilin-like signal peptide peptidase (SPP) from the most virulent human malaria parasite, Plasmodium falciparum, in the process of invasion where it has been proposed to function in the cleavage of the erythrocyte cytoskeletal protein Band 3. The role of a traditionally endoplasmic reticulum (ER) protease in the process of red blood cell invasion is unexpected. Here, using a combination of ..View full abstract
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by Australian Research Council (ARC)
We thank Alan Cowman (Walter & Eliza Hall Institute) for providing antimalarial control drugs and antibodies along with Geoffrey McFadden (University of Melbourne) who also generously provided antibodies. We thank David Riglar, Kelly Rogers and Lachlan Whitehead for their help with imaging. Human erythrocytes were kindly provided by the Red Cross Blood Bank (Melbourne). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. Funding for the research came from the National Health and Medical Research Council of Australia (NHMRC Program Grant Project Grant 637340 J. B. and S. A. R.). D. W. is supported by a Peter Doherty Australian Biomedical Fellowship from the NHMRC (APP1035715); E. S. Z. is supported by an Australian Postgraduate Award (APA) from the Australian Federal Government; J. G. B., S. A. R. and J. B. are supported through Australian Research Council (ARC) Future Fellowships (FT0992317, FT0990350 and FT100100112, respectively). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have declared that no conflict of interest exists.