Plasmodium falciparum expresses a multidrug resistance-associated protein.
Plasmodium falciparum proteins that efflux toxic metabolic products such as oxidised glutathione (GSSG) are possible targets for anti-malarial drug development. Proteins capable of transporting GSSG and glutathione conjugates include the multidrug resistance-associated transporters (MRPs). A gene, PFA0590w, encoding a MRP homologue, has been identified in P. falciparum. Here we show the presence of full-length mRNA (5.5 kb) of this PfMRP in trophozoites by RT-PCR and Northern blotting. A polyclonal anti-PfMRP antibody generated against two unique, hydrophilic peptides in the predicted sequence produced a strong immunoreactive protein band of 210-215 kDa on Western blots of schizonts of chloroquine-sensitive and chloroquine-resistant strains, confirming expression of PfMRP protein. Using confocal microscopy the protein was seen to be localised at the edge of the schizonts with no obvious staining of the food vacuole. We suggest that PfMRP may act as the GSSG transporter in the parasite plasma membrane.
Klokouzas
Antonios
A
Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK.
Tiffert
Teresa
T
van Schalkwyk
Donelly
D
Wu
Chung-Pu
CP
van Veen
Hendrik W
HW
Barrand
Margery A
MA
Hladky
Stephen B
SB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019803:Glutathione Disulfide; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D015800:Protozoan Proteins; D012333:RNA, Messenger; D019803:Glutathione Disulfide