Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding

Justin A. Boddey, Matthew T. O'Neill, Sash Lopaticki, Teresa G. Carvalho, Anthony N. Hodder, Thomas Nebl, Stephan Wawra, Pieter Van West, Zeinab Ebrahimzadeh, Dave Richard, Sven Flemming, Tobias Spielmann, Jude Pryzborski, Jeff J. Babon, Alan F. Cowman

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Abstract

Plasmodium falciparum exports proteins into erythrocytes using the Plasmodium export element (PEXEL) motif, which is cleaved in the endoplasmic reticulum (ER) by plasmepsin V (PMV). A recent study reported that phosphatidylinositol-3-phosphate (PI(3)P) concentrated in the ER binds to PEXEL motifs and is required for export independent of PMV, and that PEXEL motifs are functionally interchangeable with RxLR motifs of oomycete effectors. Here we show that the PEXEL does not bind PI(3)P, and that this lipid is not concentrated in the ER. We find that RxLR motifs cannot mediate export in P. falciparum. Parasites expressing a mutated version of KAHRP, with the PEXEL motif repositioned near the signal sequence, prevented PMV cleavage. This mutant possessed the putative PI(3)P-binding residues but is not exported. Reinstatement of PEXEL to its original location restores processing by PMV and export. These results challenge the PI(3)P hypothesis and provide evidence that PEXEL position is conserved for co-translational processing and export.
Original languageEnglish
Article number10470
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 1 Feb 2016

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    Boddey, J. A., O'Neill, M. T., Lopaticki, S., Carvalho, T. G., Hodder, A. N., Nebl, T., Wawra, S., Van West, P., Ebrahimzadeh, Z., Richard, D., Flemming, S., Spielmann, T., Pryzborski, J., Babon, J. J., & Cowman, A. F. (2016). Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding. Nature Communications, 7, 1-14. [10470]. https://doi.org/10.1038/ncomms10470