title: Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.
abstract: Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei.
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Magali
authors.initials: M
authors.lastname: Roques
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wall
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Douglass
authors.affiliation: Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Abhinay
authors.initials: A
authors.lastname: Ramaprasad
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Mbinda L
authors.initials: ML
authors.lastname: Kaindama
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Brusini
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Nimitray
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Zineb
authors.initials: Z
authors.lastname: Rchiad
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Declan
authors.initials: D
authors.lastname: Brady
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Guttery
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Sally P
authors.initials: SP
authors.lastname: Wheatley
authors.affiliation: UCL Cancer Institute, University College London, London, United Kingdom.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamano
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, Mill Hill, London, United Kingdom.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.affiliation: Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Bill
authors.initials: B
authors.lastname: Wickstead
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology*; D009033:Culicidae; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D033661:Oocysts; D010962:Plasmodium berghei / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D034101:Sporozoites / Q000254:growth & development
chemical_list: C406804:Cyc3 protein, Trypanosoma brucei; D016213:Cyclins; D015800:Protozoan Proteins