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Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis
Journal article   Open access

Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis

Tetsuya Furuya, Jianbing Mu, Karen Hayton, Anna Liu, Junhui Duan, Louis Nkrumah, Deirdre A Joy, David A Fidock, Hisashi Fujioka, Akhil B Vaidya, …
Proceedings of the National Academy of Sciences - PNAS, v 102(46), pp 16813-16818
15 Nov 2005
PMID: 16275909
url
https://doi.org/10.1073/pnas.0501858102View
Published, Version of Record (VoR) Open

Abstract

Biological Sciences gametocyte microarray genetic mapping malaria
A male gametocyte defect in the Plasmodium falciparum Dd2 parasite was previously discovered through the observation that all progeny clones in a Dd2 × HB3 genetic cross were the result of fertilization events between Dd2 female and HB3 male gametes. A determinant linked to the defect in Dd2 was subsequently mapped to an 800-kb segment on chromosome 12. Here, we report further mapping of the determinant to an 82-kb region and the identification of a candidate gene, P. falciparum male development gene 1 ( pfmdv-1 ), that is expressed at a lower level in Dd2 compared with the wild-type normal male gametocyte-producing ancestor W2. Pfmdv-1 protein is sexual-stage specific and is located on the gametocyte plasma membrane, parasitophorous vacuole membrane, and the membranes of cleft-like structures within the erythrocyte. Disruption of pfmdv-1 results in a dramatic reduction in mature gametocytes, especially functional male gametocytes, with the majority of sexually committed parasites developmentally arrested at stage I. The pfmdv-1 -knockout parasites show disturbed membrane structures, particularly multimembrane vesicles/tubes that likely derive from deformed cleft-like structures. Mosquito infectivity of the knockout parasites was also greatly reduced but not completely lost. The results suggest that pfmdv-1 plays a key role in gametocyte membrane formation and integrity.

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Collaboration types
Domestic collaboration
Web of Science research areas
Parasitology
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