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J. Biol. Chem., Vol. 277, Issue 32, 28923-28933, August 9, 2002
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From the 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.
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*
,
,
,
,
,
, and
§§
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
*
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 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.
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