title: Conditional expression of apical membrane antigen 1 in Plasmodium falciparum shows it is required for erythrocyte invasion by merozoites.
abstract: Malaria is caused by obligate intracellular parasites, of which Plasmodium falciparum is the most lethal species. In humans, P.  falciparum merozoites (invasive forms of the parasite) employ a host of parasite proteins to rapidly invade erythrocytes. One of these is the P.  falciparum apical membrane antigen 1 (PfAMA1) which forms a complex with rhoptry neck proteins at the tight junction. Here, we have placed the Pfama1 gene under conditional control using dimerizable Cre recombinase (DiCre) in P.  falciparum. DiCre-mediated excision of the loxP-flanked Pfama1 gene results in approximately 80% decreased expression of the protein within one intraerythrocytic growth cycle. This reduces growth by 40%, due to decreased invasion efficiency characterized by a post-invasion defect in sealing of the parasitophorous vacuole. These results show that PfAMA1 is an essential protein for merozoite invasion in P.  falciparum and either directly or indirectly plays a role in resealing of the red blood cell at the posterior end of the invasion event.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., 3052, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Yap
authors.forename: Mauro F
authors.initials: MF
authors.lastname: Azevedo
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gilson
authors.forename: Greta E
authors.initials: GE
authors.lastname: Weiss
authors.forename: Matthew T
authors.initials: MT
authors.lastname: O'Neill
authors.forename: Danny W
authors.initials: DW
authors.lastname: Wilson
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D004912:Erythrocytes / Q000469:parasitology*; D015870:Gene Expression; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D052940:Merozoites / Q000502:physiology*; D008967:Molecular Biology; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D014617:Vacuoles / Q000469:parasitology*
chemical_list: D000953:Antigens, Protozoan; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium