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Eukaryotic Cell, December 2008, p. 2123-2132, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00274-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Deletion of the Plasmodium falciparum Merozoite Surface Protein 7 Gene Impairs Parasite Invasion of Erythrocytes{triangledown}

Madhusudan Kadekoppala,1* Rebecca A. O'Donnell,2 Munira Grainger,1 Brendan S. Crabb,2,3 and Anthony A. Holder1

Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom,1 The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050,2 Macfarlane Burnet Institute for Medical Research & Public Health, Burnet Institute, Melbourne, VIC 3001, Australia3

Received 14 August 2008/ Accepted 17 September 2008

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 D10{Delta}MSP7 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, D10{Delta}MSP7 parasites did not show any obvious preference for alternate pathways of invasion.

* Corresponding author. Mailing address: Division of Parasitology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44-20-8816 2402. Fax: 44-20-8816 2730. E-mail: mkadeko{at}nimr.mrc.ac.uk

{triangledown} Published ahead of print on 26 September 2008.

Eukaryotic Cell, December 2008, p. 2123-2132, Vol. 7, No. 12
1535-9778/08/$08.00+0     doi:10.1128/EC.00274-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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