Malaria parasite signal peptide peptidase is an ER-resident protease required for growth but not for invasion

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dc.contributor.authorMarapana, D.
dc.contributor.authorWilson, D.
dc.contributor.authorZuccala, E.
dc.contributor.authorDekiwadia, C.
dc.contributor.authorBeeson, J.
dc.contributor.authorRalph, S.
dc.contributor.authorBaum, J.
dc.date.issued2012
dc.description.abstractThe 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.
dc.description.statementofresponsibilityDanushka S. Marapana, Danny W. Wilson, Elizabeth S. Zuccala, Chaitali D. Dekiwadia, James G. Beeson, Stuart A. Ralph and Jake Baum
dc.identifier.citationTraffic, 2012; 13(11):1457-1465
dc.identifier.doi10.1111/j.1600-0854.2012.01402.x
dc.identifier.issn1398-9219
dc.identifier.issn1600-0854
dc.identifier.orcidWilson, D. [0000-0002-5073-1405]
dc.identifier.urihttp://hdl.handle.net/2440/83602
dc.language.isoen
dc.publisherMunksgaard Int Publ Ltd
dc.relation.granthttp://purl.org/au-research/grants/arc/FT0992317
dc.relation.granthttp://purl.org/au-research/grants/arc/FT0990350
dc.relation.granthttp://purl.org/au-research/grants/arc/FT100100112
dc.relation.granthttp://purl.org/au-research/grants/arc/FT0992317
dc.relation.granthttp://purl.org/au-research/grants/arc/FT100100112
dc.rights© 2012 John Wiley & Sons A/S
dc.source.urihttps://doi.org/10.1111/j.1600-0854.2012.01402.x
dc.subjectendoplasmic reticulum
dc.subjectgamma-secretase
dc.subjectmalaria
dc.subjectmerozoite
dc.subjectmicroneme
dc.subjectPlasmodium falciparum
dc.subjectpresenilin
dc.subjectsignal peptide peptidase
dc.subjecttight junction
dc.titleMalaria parasite signal peptide peptidase is an ER-resident protease required for growth but not for invasion
dc.typeJournal article
pubs.publication-statusPublished

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