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

Dominique Dorin-Semblat, Sophie Schmitt, Jean Philippe Semblat, Audrey Sicard, Luc Reininger, JP Dean Goldring, Shelley Patterson, Neils Ben Quashie, Debopam Chakrabarti, Laurent Meijer, Christian Doerig

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36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2785-2794
Number of pages10
JournalMicrobiology-Sgm
Volume157
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

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