FN Archimer Export Format PT J TI Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle BT AF DORIN-SEMBLAT, Dominique SCHMITT, Sophie SEMBLAT, Jean-Philippe SICARD, Audrey REININGER, Luc GOLDRING, Dean PATTERSON, Shelley QUASHIE, Neils CHAKRABARTI, Debopam MEIJER, Laurent DOERIG, Christian AS 1:1,2;2:3;3:1,2;4:1,2;5:1,2;6:4;7:5;8:;9:5;10:3;11:1,2; FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:;11:; C1 Ecole Polytech Fed Lausanne, INSERM EPFL Joint Lab, Global Hlth Inst, GHI SV EPFL Stn 19, CH-1015 Lausanne, Switzerland. Univ Glasgow, Wellcome Trust Ctr Mol Parasitol, INSERM U609, Glasgow G12 8TA, Lanark, Scotland. CNRS, Biol Stn, Cell Cycle Grp, F-29680 Roscoff, Bretagne, France. Univ Kwazulu Natal, Durban, South Africa. Univ Cent Florida, Dept Mol Biol & Microbiol, Orlando, FL 32826 USA. C2 ECOLE POLYTECH FED LAUSANNE, SWITZERLAND UNIV GLASGOW, UK CNRS, FRANCE UNIV KWAZULU NATAL, SOUTH AFRICA UNIV CENT FLORIDA, USA IF 3.061 TC 28 UR https://archimer.ifremer.fr/doc/00175/28578/26965.pdf LA English DT Article AB 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. PY 2011 PD OCT SO Microbiology-sgm SN 1350-0872 PU Soc General Microbiology VL 157 UT 000296177300005 BP 2785 EP 2794 DI 10.1099/mic.0.049023-0 ID 28578 ER EF