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A P-GLYCOPROTEIN HOMOLOG OF PLASMODIUM-FALCIPARUM IS LOCALIZED ON THE DIGESTIVE VACUOLE


Cowman, AF; KARCZ, S; Galatis, D; Culvenor, JG
1991-06
JOURNAL OF CELL BIOLOGY
Journal Article
113
5
1033-1042
Resistance to chloroquine in Plasmodium falciparum bears a striking similarity to the multi-drug resistance (MDR) phenotype of mammalian tumor cells which is mediated by overexpression of P-glycoprotein. We show here that the P. falciparum homologue of the P-glycoprotein (Pghl) is a 160,000-D protein that is expressed throughout the asexual erythrocytic life cycle of the parasite. Quantitative immunoblotting analysis has shown that the protein is expressed at approximately equal levels in chloroquine resistant and sensitive isolates suggesting that overexpression of Pgh1 is not essential for chloroquine resistance. The chloroquine-resistant cloned line FAC8 however, does express approximately threefold more Pgh1 protein than other isolates which is most likely because of the increased pfmdrl gene copy number present in this isolate. Immunofluorescence and immunoelectron microscopy has demonstrated that Pgh1 is localized on the membrane of the digestive vacuole of mature parasites. This subcellular localization suggests that Pgh1 may modulate intracellular chloroquine concentrations and has important implications for the normal physiological function of this protein.
ROCKEFELLER UNIV PRESS
MULTIDRUG-RESISTANCE GENE; HUMAN MALARIA PARASITES; CHLOROQUINE RESISTANCE; ESCHERICHIA-COLI; VESICLE PH; PROTEIN; IDENTIFICATION; PYRIMETHAMINE; AMPLIFICATION; SECRETION
10.1083/jcb.113.5.1033
Refer to copyright notice on published article.

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Creation Date 1991-06-01 12:00:00