Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle

    Authors

    D. Dorin-Semblat; S. Schmitt; J. P. Semblat; A. Sicard; L. Reininger; D. Goldring; S. Patterson; N. Quashie; D. Chakrabarti; L. Meijer;C. Doerig

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    Abbreviated Journal Title

    Microbiology-(UK)

    Keywords

    MALARIA PARASITE; PROTEIN-KINASE; FUNCTIONAL-ANALYSIS; OSMIOPHILIC; BODIES; LIFE-CYCLE; CELL-CYCLE; EXPRESSION; GENOME; TRANSMISSION; COMPLETION; Microbiology

    Abstract

    The Plasmodium falciparum kinome includes a family of four protein kinases (Pfnek-1 to -4) related to the NIMA (never-in-mitosis) family, members of which play important roles in mitosis and meiosis in eukaryotic cells. Only one of these, Pfnek-1, which we previously characterized at the biochemical level, is expressed in asexual parasites. The other three (Pfnek-2, -3 and -4) are expressed predominantly in gametocytes, and a role for nek-2 and nek-4 in meiosis has been documented. Here we show by reverse genetics that Pfnek-1 is required for completion of the asexual cycle in red blood cells and that its expression in gametocytes in detectable by immunofluorescence in male (but not in female) gametocytes, in contrast with Pfnek-2 and Pfnek-4. This indicates that the function of Pfnek-1 is non-redundant with those of the other members of the Pfnek family and identifies Pfnek-1 as a potential target for antimalarial chemotherapy. A medium-throughput screen of a small-molecule library provides proof of concept that recombinant Pfnek-1 can be used as a target in drug discovery.

    Journal Title

    Microbiology-Sgm

    Volume

    157

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    2785

    Last Page

    2794

    WOS Identifier

    WOS:000296177300005

    ISSN

    1350-0872

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