title: Deletion of the Plasmodium falciparum merozoite surface protein 7 gene impairs parasite invasion of erythrocytes.
abstract: Merozoite surface proteins have been implicated in the initial attachment to the host red blood cell membrane that begins the process of invasion, an important step in the life cycle of the malaria parasite. In Plasmodium falciparum, merozoite surface proteins include several glycosylphosphatidyl inositol-anchored proteins and peripheral proteins attached to the membrane through protein-protein interactions. The most abundant of these proteins is the merozoite surface protein 1 (MSP1) complex, encoded by at least three genes: msp1, msp6, and msp7. The msp7 gene is part of a six-member multigene family in Plasmodium falciparum. We have disrupted msp7 in the Plasmodium falciparum D10 parasite, as confirmed by Southern hybridization. Immunoblot and indirect immunofluorescence analyses confirmed the MSP7 null phenotype of D10DeltaMSP7 parasites. The synthesis, distribution, and processing of MSP1 were not affected in this parasite line. The level of expression and cellular distribution of the proteins MSP1, MSP3, MSP6, MSP9, and SERA5 remained comparable to those for the parental line. Furthermore, no significant change in the expression of MSP7-related proteins, except for that of MSRP5, was detected at the transcriptional level. The lack of MSP7 was not lethal at the asexual blood stage, but it did impair invasion of erythrocytes by merozoites to a significant degree. Despite this reduction in efficiency, D10DeltaMSP7 parasites did not show any obvious preference for alternate pathways of invasion.
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. mkadeko@nimr.mrc.ac.uk
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Kadekoppala
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: O'Donnell
authors.forename: Munira
authors.initials: M
authors.lastname: Grainger
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000469:parasitology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000378:metabolism; D052940:Merozoites / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C439571:merozoite surface protein 7, Plasmodium