@article{17c886bfe6af4b9a889eaa32abd798c5,
title = "A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium",
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.",
author = "Abhinav Sinha and Hughes, {Katie R.} and Modrzynska, {Katarzyna K.} and Otto, {Thomas D.} and Claudia Pfander and Dickens, {Nicholas J.} and Religa, {Agnieszka A.} and Ellen Bushell and Graham, {Anne L.} and Rachael Cameron and Kafsack, {Bjorn F.C.} and Williams, {April E.} and Manuel Llin{\'a}s and Matthew Berriman and Oliver Billker and Waters, {Andrew P.}",
note = "Funding Information: Acknowledgements We thank A. McBride for technical assistance with mosquito transmissions; A. R. Gomes, J. Tripathi, D. Vaughan and the III flow cytometry facility for assistance; C. Cairney and N. Keith at the Beatson Institute for use of their Agilent microarray scanner; and A. Cortes and D. Baker for reading of the manuscript. A.P.W. is funded by the Wellcome Trust (ref. 083811/Z/07/Z). The Wellcome Trust Centre for Molecular Parasitology is supported by core funding from the Wellcome Trust (085349). A.S. was a student of the University of Glasgow Wellcome Trust 4-year PhD Programme Molecular Functions in Disease. A.P.W., O.B. and M.B. are members of Evimalar (ref. 242095), which funds the work of T.D.O. Work at the Sanger Institute was fundedbygrants fromthe Wellcome Trust (098051)and the MedicalResearchCouncil (G0501670). M.L. is funded by the National Institutes of Health (R01 AI076276) and the Centre for Quantitative Biology (P50GM071508). B.F.C.K. was supported by a Howard Hughes Medical Institute fellowship of the Damon Runyon Cancer Research Foundation.",
year = "2014",
doi = "10.1038/nature12970",
language = "English (US)",
volume = "507",
pages = "253--257",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7491",
}