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

Sinha, A. et al. (2014) A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature, 507(7491), pp. 253-257. (doi:10.1038/nature12970) (PMID:24572359) (PMCID:PMC4105895)

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Abstract

Commitment to and completion of sexual development are essential for malaria parasites (protists of the genus Plasmodium) to be transmitted through mosquitoes1. 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.

Item Type:Articles (Letter)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cameron, Mrs Rachael and Dickens, Dr Nicholas and Billker, Dr Oliver and Sinha, Dr Abhinav and Religa, Miss Agnieszka and Modrzynska, Dr Katarzyna and Hughes, Dr Katie and Waters, Professor Andy and Otto, Dr Thomas and Graham, Miss Anne
Authors: Sinha, A., Hughes, K. R., Modrzynska, K. K., Otto, T. D., Pfander, C., Dickens, N. J., Religa, A. A., Bushell, E., Graham, A. L., Cameron, R., Kafsack, B. F. C., Williams, A. E., Llinás, M., Berriman, M., Billker, O., and Waters, A. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature
ISSN:0028-0836
ISSN (Online):1476-4687

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