Publication Date:
2014-02-28
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105895/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105895/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sinha, Abhinav -- Hughes, Katie R -- Modrzynska, Katarzyna K -- Otto, Thomas D -- Pfander, Claudia -- Dickens, Nicholas J -- Religa, Agnieszka A -- Bushell, Ellen -- Graham, Anne L -- Cameron, Rachael -- Kafsack, Bjorn F C -- Williams, April E -- Llinas, Manuel -- Berriman, Matthew -- Billker, Oliver -- Waters, Andrew P -- 083811/Wellcome Trust/United Kingdom -- 083811/Z/07/Z/Wellcome Trust/United Kingdom -- 085349/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 104111/Wellcome Trust/United Kingdom -- G0501670/Medical Research Council/United Kingdom -- P50 GM071508/GM/NIGMS NIH HHS/ -- P50GM071508/GM/NIGMS NIH HHS/ -- R01 AI076276/AI/NIAID NIH HHS/ -- T32 GM007388/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 13;507(7491):253-7. doi: 10.1038/nature12970. Epub 2014 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8QQ, UK [2]. ; 1] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK [2]. ; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. ; Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8QQ, UK. ; Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA. ; 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA. ; 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA [3] Department of Biochemistry and Molecular Biology and Center for Infectious Disease Dynamics, The Pennsylvania State University, State College, Pennsylvania 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572359" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Culicidae/parasitology
;
DNA-Binding Proteins/deficiency/genetics/*metabolism
;
Feedback, Physiological
;
Female
;
Gene Expression Regulation
;
Germ Cells/cytology/*growth & development/metabolism
;
Malaria/*parasitology
;
Male
;
Mutation/genetics
;
Plasmodium berghei/cytology/*genetics/*physiology
;
Protein Transport
;
Protozoan Proteins/genetics/*metabolism
;
Reproduction, Asexual
;
Sexual Development/*genetics
;
Transcription, Genetic
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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