Journal article

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 Przyborski, Jeff J Babon, Alan F Cowman

NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2016

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 si..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Ramaciotti Foundation Establishment Grant


Awarded by Canadian Institutes for Health Research


Awarded by German Research Foundation


Awarded by Biotechnology and Biological Sciences Research Council


Funding Acknowledgements

We thank the Red Cross blood bank in Melbourne for human erythrocytes. We thank Svenja Gunther for expression of GBP130 66-196 proteins; Michelle Gazdik and Chris Burns for help in preparing lipids; Lachlan Whitehead (Centre for Dynamic Imaging, Walter and Eliza Hall Institute) for assistance with quantification of export; and David Bocher for help with generation of STEVOR constructs. This work was supported by the National Health and Medical Research Council of Australia (grants 637406, 1010326, 1049811 and 1057960), a Ramaciotti Foundation Establishment Grant (3197/2010), a Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS, and the Canadian Institutes for Health Research (MOP#130359). J.A.B is an Australian Research Council QEII Fellow, SF was supported by the Research Training Group GRK1459 of the German Research Foundation, and AFC is a Howard Hughes International Scholar.