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A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium.

TitleA cascade of DNA-binding proteins for sexual commitment and development in Plasmodium.
Publication TypeJournal Article
Year of Publication2014
AuthorsSinha A, Hughes KR, Modrzynska KK, Otto TD, Pfander C, Dickens NJ, Religa AA, Bushell E, Graham AL, Cameron R, Kafsack BFC, Williams AE, LlinĂ¡s M, Berriman M, Billker O, Waters AP
JournalNature
Volume507
Issue7491
Pagination253-257
Date Published2014 Mar 13
ISSN1476-4687
KeywordsAnimals, Culicidae, DNA-Binding Proteins, Feedback, Physiological, Female, Gene Expression Regulation, Germ Cells, Malaria, Male, Mutation, Plasmodium berghei, Protein Transport, Protozoan Proteins, Reproduction, Asexual, Sexual Development, Transcription, Genetic
Abstract

Commitment to and completion of sexual development are essential for malaria parasites (protists of the genus Plasmodium) to be transmitted through mosquitoes. The molecular mechanism(s) responsible for commitment have been hitherto unknown. Here we show that PbAP2-G, a conserved member of the apicomplexan AP2 (ApiAP2) family of DNA-binding proteins, is essential for the commitment of asexually replicating forms to sexual development in Plasmodium berghei, a malaria parasite of rodents. PbAP2-G was identified from mutations in its encoding gene, PBANKA_143750, which account for the loss of sexual development frequently observed in parasites transmitted artificially by blood passage. Systematic gene deletion of conserved ApiAP2 genes in Plasmodium confirmed the role of PbAP2-G and revealed a second ApiAP2 member (PBANKA_103430, here termed PbAP2-G2) that significantly modulates but does not abolish gametocytogenesis, indicating that a cascade of ApiAP2 proteins are involved in commitment to the production and maturation of gametocytes. The data suggest a mechanism of commitment to gametocytogenesis in Plasmodium consistent with a positive feedback loop involving PbAP2-G that could be exploited to prevent the transmission of this pernicious parasite.

DOI10.1038/nature12970
Alternate JournalNature
PubMed ID24572359
PubMed Central IDPMC4105895
Grant ListG0501670 / / Medical Research Council / United Kingdom
085349 / / Wellcome Trust / United Kingdom
P50GM071508 / GM / NIGMS NIH HHS / United States
083811/Z/07/Z / / Wellcome Trust / United Kingdom
R01 AI076276 / AI / NIAID NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
098051 / / Wellcome Trust / United Kingdom
/ / Howard Hughes Medical Institute / United States
104111 / / Wellcome Trust / United Kingdom
083811 / / Wellcome Trust / United Kingdom

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