title: Alteration of the parasite plasma membrane and the parasitophorous vacuole membrane during exo-erythrocytic development of malaria parasites.
abstract: The rodent malaria parasite Plasmodium berghei develops in hepatocytes within 48-52h from a single sporozoite into up to 20,000 daughter parasites, so-called merozoites. The cellular and molecular details of this extensive proliferation are still largely unknown. Here we have used a transgenic, RFP-expressing P. berghei parasite line and molecular imaging techniques including intravital microscopy to decipher various aspects of parasite development within the hepatocyte. In late schizont stages, MSP1 is expressed and incorporated into the parasite plasma membrane that finally forms the membrane of developing merozoites by continuous invagination steps. We provide first evidence for activation of a verapamil-sensitive Ca(2+) channel in the plasma membrane of liver stage parasites before invagination occurs. During merozoite formation, the permeability of the parasitophorous vacuole membrane changes considerably before it finally becomes completely disrupted, releasing merozoites into the host cell cytoplasm.
authors.affiliation: Bernhard Nocht Institute For Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Sturm
authors.forename: Stefanie
authors.initials: S
authors.lastname: Graewe
authors.forename: Blandine
authors.initials: B
authors.lastname: Franke-Fayard
authors.forename: Silke
authors.initials: S
authors.lastname: Retzlaff
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bolte
authors.forename: Bernhard
authors.initials: B
authors.lastname: Roppenser
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
authors.forename: Chris
authors.initials: C
authors.lastname: Janse
authors.forename: Volker
authors.initials: V
authors.lastname: Heussler
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000469:parasitology*; D052940:Merozoites / Q000254:growth & development; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence / Q000379:methods; D010962:Plasmodium berghei / Q000254:growth & development*; D051381:Rats; D034101:Sporozoites / Q000254:growth & development; D014617:Vacuoles / Q000378:metabolism*; D014700:Verapamil
chemical_list: D015220:Calcium Channels; D014700:Verapamil