Defining the morphology and mechanism of the hemoglobin transport pathway in Plasmodium falciparum-infected erythrocytes.
Hemoglobin degradation during the asexual cycle of Plasmodium falciparum is an obligate process for parasite development and survival. It is established that hemoglobin is transported from the host erythrocyte to the parasite digestive vacuole (DV), but this biological process is not well characterized. Three-dimensional reconstructions made from serial thin-section electron micrographs of untreated, trophozoite-stage P. falciparum-infected erythrocytes (IRBC) or IRBC treated with different pharmacological agents provide new insight into the organization and regulation of the hemoglobin transport pathway. Hemoglobin internalization commences with the formation of cytostomes from localized, electron-dense collars at the interface of the parasite plasma and parasitophorous vacuolar membranes. The cytostomal collar does not function as a site of vesicle fission but rather serves to stabilize the maturing cytostome. We provide the first evidence that hemoglobin transport to the DV uses an actin-myosin motor system. Short-lived, hemoglobin-filled vesicles form from the distal end of the cytostomes through actin and dynamin-mediated processes. Results obtained with IRBC treated with N-ethylmaleimide (NEM) suggest that fusion of hemoglobin-containing vesicles with the DV may involve a soluble NEM-sensitive factor attachment protein receptor-dependent mechanism. In this report, we identify new key components of the hemoglobin transport pathway and provide a detailed characterization of its morphological organization and regulation.
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Katharine J
KJ
Milani
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Timothy G
TG
Schneider
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA Theodore.Taraschi@jefferson.edu.
Theodore F
TF
Taraschi
D000199:Actins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology* / Q000648:ultrastructure; D006454:Hemoglobins / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D015388:Organelles / Q000378:metabolism; D010963:Plasmodium falciparum / Q000472:pathogenicity* / Q000648:ultrastructure; D053058:Trophozoites / Q000378:metabolism
D000199:Actins; D006454:Hemoglobins