Title

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

Authors

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

Comments

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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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