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.
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Katie R
authors.initials: KR
authors.lastname: Hughes
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Katarzyna K
authors.initials: KK
authors.lastname: Modrzynska
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Otto
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pfander
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Dickens
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Religa
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Bushell
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Graham
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Rachael
authors.initials: R
authors.lastname: Cameron
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
authors.forename: Bjorn F C
authors.initials: BFC
authors.lastname: Kafsack
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: April E
authors.initials: AE
authors.lastname: Williams
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.|Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Llinas
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Waters
mesh_terms: D000818:Animals; D009033:Culicidae / Q000469:parasitology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008288:Malaria / Q000469:parasitology*; D008297:Male; D009154:Mutation / Q000235:genetics; D010962:Plasmodium berghei / Q000166:cytology / Q000235:genetics* / Q000502:physiology*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012100:Reproduction, Asexual; D046468:Sexual Development / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D015800:Protozoan Proteins