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, which we term 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.
authors.affiliation: Department of Cell Biology and Anatomy, University of Arizona College of Medicine, Tucson, AZ 85724, USA. elliott@arizona.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Elliott
authors.forename: Michael T
authors.initials: MT
authors.lastname: McIntosh
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Gina
authors.initials: G
authors.lastname: Zhang
authors.forename: Pavlina
authors.initials: P
authors.lastname: Baevova
authors.forename: Keith A
authors.initials: KA
authors.lastname: Joiner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D006454:Hemoglobins / Q000378:metabolism* / Q000648:ultrastructure; D008288:Malaria / Q000469:parasitology*; D016253:Microscopy, Immunoelectron; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000648:ultrastructure; D052939:Schizonts / Q000648:ultrastructure; D053058:Trophozoites / Q000648:ultrastructure; D014617:Vacuoles / Q000648:ultrastructure; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D006454:Hemoglobins; D020696:rab5 GTP-Binding Proteins