Arrest of Nuclear Division in Plasmodium through Blockage of Erythrocyte Surface Exposed Ribosomal Protein P2

PLoS Pathogens

Rita Tewari¹  Shobhona Sharma²  Reshma Korde²  Sudipta Das²  Himanish Basu² 

[1] Centre for Genetics and Genomics, Queen's Medical Centre, The University of Nottingham, Nottingham, United Kingdom;Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India

关键词: Plasmodium;    Parasitic diseases;    Cell cycle;    cell division;    DAPI staining;    Red blood cells;    Cell staining;    Flow cytometry;    Plasmodium falciparum;   

DOI  :  10.1371/journal.ppat.1002858

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Malaria parasites reside inside erythrocytes and the disease manifestations are linked to the growth inside infected erythrocytes (IE). The growth of the parasite is mostly confined to the trophozoite stage during which nuclear division occurs followed by the formation of cell bodies (schizogony). The mechanism and regulation of schizogony are poorly understood. Here we show a novel role for a Plasmodium falciparum 60S stalk ribosomal acidic protein P2 (PfP2) (PFC0400w), which gets exported to the IE surface for 6–8 hrs during early schizogony, starting around 26–28 hrs post-merozoite invasion. The surface exposure is demonstrated using multiple PfP2-specific monoclonal antibodies, and is confirmed through transfection using PfP2-GFP. The IE surface-exposed PfP2-protein occurs mainly as SDS-resistant P2-homo-tetramers. Treatment with anti-PfP2 monoclonals causes arrest of IEs at the first nuclear division. Upon removal of the antibodies, about 80–85% of synchronized parasites can be released even after 24 hrs of antibody treatment. It has been reported that a tubovesicular network (TVN) is set up in early trophozoites which is used for nutrient import. Anti-P2 monoclonal antibodies cause a complete fragmentation of TVN by 36 hrs, and impairs lipid import in IEs. These may be downstream causes for the cell-cycle arrest. Upon antibody removal, the TVN is reconstituted, and the cell division progresses. Each of the above properties is observed in the rodent malaria parasite species P. yoelii and P. berghei. The translocation of the P2 protein to the IE surface is therefore likely to be of fundamental importance in Plasmodium cell division.

【 授权许可】

CC BY