ghosh-cysteineprotease-2018.pdf (27.81 MB)
The cysteine protease dipeptidyl aminopeptidase 3 does not contribute to egress of Plasmodium falciparum from host red blood cells
journal contribution
posted on 2018-03-06, 00:00 authored by Sreejoyee Ghosh, Scott Chisholm, Madeline Dans, Asha Lakkavaram, Kit Kennedy, Stuart A Ralph, Natalie CounihanNatalie Counihan, Tania De Koning-WardTania De Koning-WardThe ability of Plasmodium parasites to egress from their host red blood cell is critical for the amplification of these parasites in the blood. Previous forward chemical genetic approaches have implicated the subtilisin-like protease (SUB1) and the cysteine protease dipeptidyl aminopeptidase 3 (DPAP3) as key players in egress, with the final step of SUB1 maturation thought to be due to the activity of DPAP3. In this study, we have utilized a reverse genetics approach to engineer transgenic Plasmodium falciparum parasites in which dpap3 expression can be conditionally regulated using the glmS ribozyme based RNA-degrading system. We show that DPAP3, which is expressed in schizont stages and merozoites and localizes to organelles distinct from the micronemes, rhoptries and dense granules, is not required for the trafficking of apical proteins or processing of SUB1 substrates, nor for parasite maturation and egress from red blood cells. Thus, our findings argue against a role for DPAP3 in parasite egress and indicate that the phenotypes observed with DPAP3 inhibitors are due to off-target effects.
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Journal
PLoS oneVolume
13Issue
3Article number
e0193538Pagination
1 - 16Publisher
Public Library of ScienceLocation
San Francisco, Calif.Publisher DOI
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eISSN
1932-6203Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2018, Ghosh et al.Usage metrics
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