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

Abhinav Sinha, Katie R. Hughes, Katarzyna K. Modrzynska, Thomas D. Otto, Claudia Pfander, Nicholas J. Dickens, Agnieszka A. Religa, Ellen Bushell, Anne L. Graham, Rachael Cameron, Bjorn F. C. Kafsack, April E. Williams, Manuel Llinás, Matthew Berriman, Oliver Billker, Andrew P. Waters

Research output: Contribution to journalArticle

184 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)253–257
Number of pages5
JournalNature
Volume507
Issue number7491
DOIs
Publication statusPublished - 13 Mar 2014

Keywords

  • animals
  • culicidae
  • DNA-binding proteins
  • physiological feedback
  • female
  • gene expression regulation
  • germ cells
  • malaria
  • male
  • mutation
  • plasmodium berghei
  • protein transport
  • protozoan proteins
  • asexual reproduction
  • sexual development
  • genetic transcription

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