Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle
|Author(s)||Dorin-Semblat Dominique1, 2, Schmitt Sophie3, Semblat Jean-Philippe1, 2, Sicard Audrey1, 2, Reininger Luc1, 2, Goldring Dean4, Patterson Shelley5, Quashie Neils, Chakrabarti Debopam5, Meijer Laurent3, Doerig Christian1, 2|
|Affiliation(s)||1 : Ecole Polytech Fed Lausanne, INSERM EPFL Joint Lab, Global Hlth Inst, GHI SV EPFL Stn 19, CH-1015 Lausanne, Switzerland.
2 : Univ Glasgow, Wellcome Trust Ctr Mol Parasitol, INSERM U609, Glasgow G12 8TA, Lanark, Scotland.
3 : CNRS, Biol Stn, Cell Cycle Grp, F-29680 Roscoff, Bretagne, France.
4 : Univ Kwazulu Natal, Durban, South Africa.
5 : Univ Cent Florida, Dept Mol Biol & Microbiol, Orlando, FL 32826 USA.
|Source||Microbiology-sgm (1350-0872) (Soc General Microbiology), 2011-10 , Vol. 157 , P. 2785-2794|
|WOS© Times Cited||26|
|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.|