Arrest of nuclear division in Plasmodium through blockage of erythrocyte surface exposed ribosomal protein P2
Authors: Shobhona Sharma
Sudipta Das
Reshma Korde
Rita Tewari
Himanish Basu
Journal: PLoS Pathogens (2012)
Discipline: MICROBIOLOGY
Keywords: Malaria parasites; erythrocytes; infected erythrocytes; Plasmodium falciparum; schizogony
Affiliations: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.

Abstract:  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. 

Retracted: No

PubPeer comments:
 This paper has an August 2012 correction for incorrect references. A possible concern with Figure 3A was pointed out to me by a reader. * Green vertical arrows: Possible splices observed in blot panels in Figure 3A II * Blue arrows: One band in the Actin blot of I (representing 24h) looks similar to a band in the Actin blot of II (representing 12h) * Red arrows: Two bands in the Actin blot of I (representing 36 and 42h) look similar to bands in the Actin blot of II (representing 24 and 30h) ![file] , 
 In the PloS Pathogens paper (Das et al 2012) the discrepancy appears to be mainly for the beta-actin Panels in Fig. 3A I and 3A II. The Pub-peer comment states that there has been splicing, and that the same data is shown for different time points. For the Panel of Figure 3A II, the same set of parasite extract blot of Panel 3A I (probed with anti-PfP2 and anti-beta actin) was probed with different antibodies (anti-MSP, anti-Enolase and anti-PCNA). We actually do not need to show beta actin Panel in 3A II, and hence we will remove the strip. The 12 hr point may have been damaged in repeated probing and perhaps had to be done separately for MSP and enolase. We are correcting Panel 3A II and will correspond with PloS Pathogens for an erratum. Once we do so we will put in an update in Pub-peer. Shobhona Sharma ,