Malaria Parasite Signal Peptide Peptidase is an ER-Resident Protease Required for Growth but not for Invasion
Details
Publication Year 2012-11, Volume 13, Issue #11, Page 1457-1465
Journal Title
TRAFFIC
Publication Type
Journal Article
Abstract
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 PfSPP 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 PfSPP plays no role in erythrocyte invasion. Nonetheless, PfSPP 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.
Publisher
WILEY-BLACKWELL
Keywords
PLASMODIUM-FALCIPARUM MEROZOITES; ERYTHROCYTE INVASION; ASPARTIC PROTEASE; MOVING JUNCTION; BINDING-PROTEIN; MEMBRANE; PRESENILIN; IDENTIFICATION; LOCALIZATION; CLEAVAGE
WEHI Research Division(s)
Infection And Immunity
Rights Notice
© 2012 John Wiley & Sons A/S


Creation Date: 2012-11-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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