Dynamin like protein 1 participated in the hemoglobin uptake pathway of Plasmodium falciparum.
BACKGROUND
During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite's hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms.


METHODS
The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 (PfDYN1) and 2 (PfDYN2) GTPase domain, were expressed in E.coli and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway.


RESULTS
The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 micromol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intracellular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment.


CONCLUSIONS
Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. falciparum and suggest its possibility of being a novel target for malaria chemotherapy.
Zhou
Hong-chang
HC
Department of Microbiology and Parasitology, Institute of Basic Medical Sciences, Peking Union Medical College, Beijing, China.
Gao
Yu-hui
YH
Zhong
Xiang
X
Wang
Heng
H
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D034281:Dynamins / Q000037:antagonists & inhibitors; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006835:Hydrazones / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000962:Antimalarials; D006454:Hemoglobins; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D034281:Dynamins