title: A malaria parasite-encoded vacuolar H(+)-ATPase is targeted to the host erythrocyte.
abstract: The asexual development of malaria parasites inside the erythrocyte is accompanied by changes in the composition, structure, and function of the host cell membrane and cytoplasm. The parasite exports a membrane network into the host cytoplasm and several proteins that are inserted into the erythrocyte membrane, although none of these proteins has been shown to have enzymatic activity. We report here that a functional malaria parasite-encoded vacuolar (V)-H(+)-ATPase is exported to the erythrocyte and localized in membranous structures and in the plasma membrane of the infected erythrocyte. This localization was determined by separation of parasite and erythrocyte membranes and determination of enzyme marker activities and by immunofluorescence microscopy assays using antibodies against the B subunit of the malarial V-H(+)-ATPase and erythrocyte (spectrins) and parasite (merozoite surface protein 1) markers. Our results suggest that this pump has a role in the maintenance of the intracellular pH (pH(i)) of the infected erythrocyte. Our results also indicate that although the pH(i) maintained by the V-H(+)-ATPase is important for maximum uptake of small metabolites at equilibrium, it does not appear to affect transport across the erythrocyte membrane and is, therefore, not involved in the previously described phenomenon of increased permeability of infected erythrocytes that is sensitive to chloride channel inhibitors (new permeation pathway). This constitutes the first report of the presence of a functional enzyme of parasite origin in the plasma membrane of its host.
authors.affiliation: Department of Pathobiology and Center for Zoonoses Research, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
authors.forename: Norma
authors.initials: N
authors.lastname: Marchesini
authors.forename: Mauricio
authors.initials: M
authors.lastname: Vieira
authors.forename: Shuhong
authors.initials: S
authors.lastname: Luo
authors.forename: Silvia N J
authors.initials: SN
authors.lastname: Moreno
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000494:pharmacology; D008288:Malaria / Q000201:enzymology*; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010962:Plasmodium berghei / Q000201:enzymology*; D010963:Plasmodium falciparum / Q000201:enzymology*; D013049:Spectrin / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D018942:Macrolides; D020066:Merozoite Surface Protein 1; C057620:bafilomycin A; D013049:Spectrin; D025262:Vacuolar Proton-Translocating ATPases