TY - JOUR
T1 - Plasmodium falciparum NIMA-related kinase Pfnek-1
T2 - Sex specificity and assessment of essentiality for the erythrocytic asexual cycle
AU - Dorin-Semblat, Dominique
AU - Schmitt, Sophie
AU - Semblat, Jean Philippe
AU - Sicard, Audrey
AU - Reininger, Luc
AU - Goldring, JP Dean
AU - Patterson, Shelley
AU - Quashie, Neils Ben
AU - Chakrabarti, Debopam
AU - Meijer, Laurent
AU - Doerig, Christian
PY - 2011/10
Y1 - 2011/10
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=80053440912&partnerID=8YFLogxK
U2 - 10.1099/mic.0.049023-0
DO - 10.1099/mic.0.049023-0
M3 - Article
C2 - 21757488
AN - SCOPUS:80053440912
SN - 1350-0872
VL - 157
SP - 2785
EP - 2794
JO - Microbiology
JF - Microbiology
IS - 10
ER -