A role of falcipain-2, principal cysteine proteases of Plasmodium falciparum in merozoite egression.
The process of merozoite release in Plasmodium falciparum involves rupture of the parasitophorous vacuole membrane and erythrocyte plasma membrane. Through the use of protease inhibitors that halt the merozoite release, a number of parasite proteases, especially serine, aspartic, and cysteine proteases, have been implicated in the schizont rupture. To understand the precise role of cysteine proteases in the merozoite release, in the present study, we treated P. falciparum cultures with siRNAs corresponding to falcipain-1, falcipain-2, and falcipain-3, the three papain-family proteases of the parasite. Treatment of malaria parasites with either of the falcipain siRNAs considerably reduced parasite growth. Morphological examination of the siRNA treated parasite cultures revealed that most of the parasites in falcipain-2 siRNA treated cultures were arrested at schizont stage. Analysis of a transgenic P. falciparum line expressing chimeric-GFP upon treatment with falcipain-2 siRNA revealed block in the rupture of erythrocyte membrane at the time of merozoite egression. These results suggest that falcipain-2 is an important parasitic protease that participates in hemoglobin degradation and in the merozoite release.
Dasaradhi
Palakodeti V N
PV
International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Mohmmed
Asif
A
Kumar
Amit
A
Hossain
Manzar J
MJ
Bhatnagar
Raj K
RK
Chauhan
Virander S
VS
Malhotra
Pawan
P
D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000469:parasitology*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000201:enzymology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C443101:falcipain 3