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Malaria Parasite Signal Peptide Peptidase is an ER ‐Resident Protease Required for Growth but not for Invasion
Author(s) -
Marapana Danushka S.,
Wilson Danny W.,
Zuccala Elizabeth S.,
Dekiwadia Chaitali D.,
Beeson James G.,
Ralph Stuart A.,
Baum Jake
Publication year - 2012
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2012.01402.x
Subject(s) - biology , plasmodium falciparum , endoplasmic reticulum , malaria , microbiology and biotechnology , parasite hosting , signal peptide , protease , biochemistry , peptide sequence , immunology , enzyme , gene , world wide web , computer science
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 molecular, cellular and chemical approaches we provide evidence that Pf SPP is, instead, a bona fide ER ‐resident peptidase that remains intracellular throughout the invasion process. Furthermore, SPP ‐specific drug inhibition has no effect on erythrocyte invasion whilst having low micromolar potency against intra‐erythrocytic development. Contrary to previous reports, these results show that Pf SPP plays no role in erythrocyte invasion. Nonetheless, Pf SPP clearly represents a potential chemotherapeutic target to block parasite growth, supporting ongoing efforts to develop antimalarial‐targeting protein maturation and trafficking during intra‐erythrocytic development.