Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum

David A. Elliott, Michael T. McIntosh, Howard D. Hosgood, Shuo Chen, Gina Zhang, Pavlina Baevova, Keith A. Joiner

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, whichweterm the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment - the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.

Original languageEnglish (US)
Pages (from-to)2463-2468
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number7
DOIs
StatePublished - Feb 19 2008
Externally publishedYes

Fingerprint

Falciparum Malaria
Actins
Parasites
Hemoglobins
Polymerization
rab5 GTP-Binding Proteins
Parasitic Diseases
Plasmodium
Antimalarials
Endocytosis
Vacuoles
Phagocytosis
Malaria
Electron Microscopy
Cytoplasm
Erythrocytes
Food
Therapeutics

Keywords

  • Actin
  • Cytosome
  • Endocytosis
  • Food vacuole
  • Transport

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum. / Elliott, David A.; McIntosh, Michael T.; Hosgood, Howard D.; Chen, Shuo; Zhang, Gina; Baevova, Pavlina; Joiner, Keith A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 7, 19.02.2008, p. 2463-2468.

Research output: Contribution to journalArticle

Elliott, David A. ; McIntosh, Michael T. ; Hosgood, Howard D. ; Chen, Shuo ; Zhang, Gina ; Baevova, Pavlina ; Joiner, Keith A. / Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 7. pp. 2463-2468.
@article{04c0e7a0de114b0bb1e991deecc1ea3f,
title = "Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum",
abstract = "During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, whichweterm the {"}Big Gulp,{"} appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment - the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.",
keywords = "Actin, Cytosome, Endocytosis, Food vacuole, Transport",
author = "Elliott, {David A.} and McIntosh, {Michael T.} and Hosgood, {Howard D.} and Shuo Chen and Gina Zhang and Pavlina Baevova and Joiner, {Keith A.}",
year = "2008",
month = "2",
day = "19",
doi = "10.1073/pnas.0711067105",
language = "English (US)",
volume = "105",
pages = "2463--2468",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "7",

}

TY - JOUR

T1 - Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum

AU - Elliott, David A.

AU - McIntosh, Michael T.

AU - Hosgood, Howard D.

AU - Chen, Shuo

AU - Zhang, Gina

AU - Baevova, Pavlina

AU - Joiner, Keith A.

PY - 2008/2/19

Y1 - 2008/2/19

N2 - During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, whichweterm the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment - the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.

AB - During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, whichweterm the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment - the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.

KW - Actin

KW - Cytosome

KW - Endocytosis

KW - Food vacuole

KW - Transport

UR - http://www.scopus.com/inward/record.url?scp=40649122026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40649122026&partnerID=8YFLogxK

U2 - 10.1073/pnas.0711067105

DO - 10.1073/pnas.0711067105

M3 - Article

C2 - 18263733

AN - SCOPUS:40649122026

VL - 105

SP - 2463

EP - 2468

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 7

ER -