title: Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding.
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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Boddey
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: O'Neill
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Sash
authors.initials: S
authors.lastname: Lopaticki
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Carvalho
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hodder
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nebl
authors.affiliation: Aberdeen Oomycete Laboratory, College of Life Sciences and Medicine, University of Aberdeen-Foresterhill, Aberdeen, Scotland AB25 2ZD, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wawra
authors.affiliation: Aberdeen Oomycete Laboratory, College of Life Sciences and Medicine, University of Aberdeen-Foresterhill, Aberdeen, Scotland AB25 2ZD, UK.
authors.forename: Pieter
authors.initials: P
authors.lastname: van West
authors.affiliation: Faculté de Médecine, Université Laval, Québec City, Québec, Canada G1V4G2.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Ebrahimzadeh
authors.affiliation: Faculté de Médecine, Université Laval, Québec City, Québec, Canada G1V4G2.
authors.forename: Dave
authors.initials: D
authors.lastname: Richard
authors.affiliation: Parasitology Section, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Flemming
authors.affiliation: Parasitology Section, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Spielmann
authors.affiliation: Department of Parasitology, Philipps University Marburg , Marburg 35043, Germany.
authors.forename: Jude
authors.initials: J
authors.lastname: Przyborski
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Jeff J
authors.initials: JJ
authors.lastname: Babon
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D020816:Amino Acid Motifs; D002462:Cell Membrane; D004926:Escherichia coli; D061466:Lopinavir / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018129:Phosphatidylinositol Phosphates; D015800:Protozoan Proteins; C055525:phosphatidylinositol 3-phosphate; D061466:Lopinavir
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