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    Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes

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    Type
    Article
    Authors
    Roques, Magali
    Wall, Richard J.
    Douglass, Alexander P.
    Ramaprasad, Abhinay cc
    Ferguson, David J. P.
    Kaindama, Mbinda L.
    Brusini, Lorenzo
    Joshi, Nimitray
    Rchiad, ‍Zineb cc
    Brady, Declan
    Guttery, David S.
    Wheatley, Sally P.
    Yamano, Hiroyuki
    Holder, Anthony A. cc
    Pain, Arnab cc
    Wickstead, Bill
    Tewari, Rita
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2015-11-13
    Permanent link to this record
    http://hdl.handle.net/10754/583929
    
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    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.
    Citation
    Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes 2015, 11 (11):e1005273 PLOS Pathogens
    Publisher
    Public Library of Science (PLoS)
    Journal
    PLOS Pathogens
    DOI
    10.1371/journal.ppat.1005273
    PubMed ID
    26565797
    Additional Links
    http://dx.plos.org/10.1371/journal.ppat.1005273
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.ppat.1005273
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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