title: A perforin-like protein mediates disruption of the erythrocyte membrane during egress of Plasmodium berghei male gametocytes.
abstract: Successful gametogenesis of the malaria parasite depends on egress of the gametocytes from the erythrocytes within which they developed. Egress entails rupture of both the parasitophorous vacuole membrane and the erythrocyte plasma membrane, and precedes the formation of the motile flagellated male gametes in a process called exflagellation. We show here that egress of the male gametocyte depends on the function of a perforin-like protein, PPLP2. A mutant of Plasmodium berghei lacking PPLP2 displayed abnormal exflagellation; instead of each male gametocyte forming eight flagellated gametes, it produced gametocytes with only one, shared thicker flagellum. Using immunofluorescence and transmission electron microscopy analysis, and phenotype rescue with saponin or a pore-forming toxin, we conclude that rupture of the erythrocyte membrane is blocked in the mutant. The parasitophorous vacuole membrane, on the other hand, is ruptured normally. Some mutant parasites are still able to develop in the mosquito, possibly because the vigorous motility of the flagellated gametes eventually leads to escape from the persisting erythrocyte membrane. This is the first example of a perforin-like protein in Plasmodium parasites having a role in egress from the host cell and the first parasite protein shown to be specifically required for erythrocyte membrane disruption during egress.
authors: Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Greece.
authors: Elena
authors: E
authors: Deligianni
authors: Rhiannon N
authors: RN
authors: Morgan
authors: Lucia
authors: L
authors: Bertuccini
authors: Christine C
authors: CC
authors: Wirth
authors: Natalie C
authors: NC
authors: Silmon de Monerri
authors: Lefteris
authors: L
authors: Spanos
authors: Michael J
authors: MJ
authors: Blackman
authors: Christos
authors: C
authors: Louis
authors: Gabriele
authors: G
authors: Pradel
authors: Inga
authors: I
authors: Siden-Kiamos
mesh_terms: D000818:Animals; D004910:Erythrocyte Membrane / Q000469:parasitology*; D004912:Erythrocytes / Q000469:parasitology; D005854:Germ Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D054353:Perforin / Q000378:metabolism*; D010641:Phenotype; D010962:Plasmodium berghei / Q000187:drug effects / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology; D013081:Sperm Motility / Q000502:physiology; D013082:Sperm Tail / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
chemical_list: D015800:Protozoan Proteins; D012503:Saponins; D054353:Perforin