Microtubules in Plasmodium falciparum merozoites and their importance for invasion of erythrocytes.
Plasmodium falciparum merozoites have an array of 2-3 subpellicular microtubules, designated f-MAST. We have previously shown that colchicine inhibits merozoite invasion of erythrocytes, indicating a microtubular involvement in this process. Colchicine inhibition of invasion was reduced by the Taxol-stabilization of merozoite microtubules prior to colchicine exposure. Immunofluorescence assays showed that the number and length of f-MASTs were reduced in colchicine-treated merozoites, confirming that microtubules were the target of colchicine inhibition. The dinitroaniline drugs, trifluralin and pendimethalin, were shown by immunofluorescence to depolymerize the f-MAST and both drugs were inhibitory in invasion assays. These results demonstrate that the integrity of the f-MAST is important for successful invasion. Fluorescence imaging demonstrated the alignment of mitochondria to f-MAST, suggesting that mitochondrial transport might be perturbed in merozoites with disorganized f-MAST. Depolymerizing mt in late-stage schizonts did not affect the allocation of mitochondria to merozoites.
Fowler
R E
RE
Department of Immunology, UMDS, Medical School, Guy's Hospital, London, UK.
Fookes
R E
RE
Lavin
F
F
Bannister
L H
LH
Mitchell
G H
GH
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D003078:Colchicine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology*; D019084:Fluorescent Antibody Technique, Indirect; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D013997:Time Factors; D014274:Trifluralin / Q000494:pharmacology
D000814:Aniline Compounds; D014274:Trifluralin; D017239:Paclitaxel; D003078:Colchicine; C030856:pendimethalin