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Originally published In Press as doi:10.1074/jbc.M201968200 on May 22, 2002

J. Biol. Chem., Vol. 277, Issue 32, 28923-28933, August 9, 2002
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trans Expression of a Plasmodium falciparum Histidine-rich Protein II (HRPII) Reveals Sorting of Soluble Proteins in the Periphery of the Host Erythrocyte and Disrupts Transport to the Malarial Food Vacuole*

Thomas AkompongDagger , Madhusudan KadekoppalaDagger , Travis HarrisonDagger , Anna Oksman§, Daniel E. Goldberg§, Hisashi Fujioka||, Benjamin U. SamuelDagger , David Sullivan**Dagger Dagger , and Kasturi HaldarDagger §§

From the Dagger  Departments of Pathology and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, § Howard Hughes Medical Institute, Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, || Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, and ** The W. Harry Feinstone Department of Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205

The heme polymer hemozoin is produced in the food vacuole (fv) of the parasite after hemoglobin proteolysis and is the target of the drug chloroquine. A candidate heme polymerase, the histidine-rich protein II (HRPII), is proposed to be delivered to the fv by ingestion of the infected-red cell cytoplasm. Here we show that 97% of endogenous Plasmodium falciparum (Pf) HRPII (PfHRPII) is secreted as soluble protein in the periphery of the red cell and avoids endocytosis by the parasite, and 3% remains membrane-bound within the parasite. Transfected cells release 90% of a soluble transgene PfHRPIImyc into the red cell periphery and contain 10% membrane bound within the parasite. Yet these cells show a minor reduction in hemozoin production and IC50 for chloroquine. They also show decreased transport of resident fv enzyme PfPlasmepsin I, the endoplasmic reticulum (ER) marker PfBiP, and parasite-associated HRPII to fvs. Instead, all three proteins accumulate in the ER, although there is no defect in protein export from the parasite. The data suggest that novel mechanisms of sorting (i) soluble antigens like HRPII in the red cell cytoplasm and (ii) fv-bound membrane complexes in the ER regulate parasite digestive processes.


* This work was supported by National Institutes of Health Grants AI26670 and HL69630 (to K. H.) and AI47798 (to D. E. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of Burroughs Wellcome Scholar Award in Molecular Parasitology.

Dagger Dagger Recipient of Burroughs Wellcome Career Award and a Pew Scholar Award.

§§ Recipient of Burroughs Wellcome New Initiatives in Malaria Award. To whom correspondence should be addressed. Tel.: 312-503-0224; E-mail: k-haldar@northwestern.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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