dimnp

Team Plasmodium and Toxoplasma: membrane biogenesis and host cell–parasite interactions


Remodelling of the host cell by Plasmodium falciparum blood stages

PhotoCBB depart contact200Principal investigator : Catherine BRAUN-BRETON Professor University Montpellier

 

Team

BRAUN-BRETON Catherine

Professor UM

cbb arobase univ-montp2.fr

RUBIO Eliane

AJTP CNRS

eliane.rubio arobase univ-montp2.fr

VIALLA Emilie

AI CNRS

emile.vialla arobase univ-montp2.fr

 

e quipeCBB

The human malaria parasite Plasmodium falciparum has developed a number of fascinating cell biological processes, in response to its parasitic life style. Of particular interest are the mechanisms underpinning host erythrocyte remodeling. During its intra-erythrocytic development, P. falciparum extensively alters the functional and structural properties of the infected erythrocyte by exporting proteins into its host cell.

adapted from Maier et al. Nature Rev. Microbiol 2009RBCremodelling-web

Some of these proteins are exported to the host cell membrane generating electron-dense protrusions (referred to as knobs) at the parasitized red blood cell surface that mediate cytoadherence of infected erythrocytes to the microvasculature endothelium, and therefore contribute to the pathogenesis of severe malaria and to immune evasion. Others are exported to the host cell cytosol upon and/or post invasion, contributing to modifications of host cell proteins and to the establishment of a parasite membranous compartment referred to as Maurer’s clefts in the host cell cytoplasm. In addition, the parasite recruits human proteins that contribute, in interaction with exported parasite proteins, to the host cell remodeling as we have shown for the human LANCL1 peripheral membrane protein.

Proteomic studies of infected erythrocyte (iRBC) ghosts have suggested important roles for the Maurer’s clefts in cell signalling, phospholipid biosynthesis and, possibly, other biochemical pathways in addition to their role in protein trafficking to the RBC plasma membrane. The Maurer’s cleft is a novel compartment, unique to Plasmodium and playing crucial roles for the parasite erythrocytic development and its pathogenicity. We hypothesize that it constitutes a marshal platform for both parasite and host proteins displaying important functions in the host cell cytoplasm and plasma membrane.

We are currently continuing our pioneering work on these structures and focusing on their biogenesis (kinetics of formation, delivery of protein and lipid constituents) with the aim of unraveling at the molecular level, the mechanisms central to their formation and biological activity (delivery of parasite proteins to the red cell membrane, binding to the red cell membrane, recruitment of host proteins). In collaboration with physicists at UM2, we are also focusing our studies on the parasite-induced modifications of the RBC membrane central to parasite entry and parasite egress and the relevance of phosphorylation events for these processes.


 

Recent references related to the project

Blisnick, T., Vincensini, L., Fall, G. and Braun Breton, C. (2006). PP1 phosphatase, a Plasmodium falciparum essential enzyme, is exported to the host cell and implicated in the release of infectious merozoites. Cell. Microbiol. 8 : 591 - 601

Lanzer, M., Wickert, H., Krohne, G., Vincensini, L., and Braun Breton, C. (2006). Maurer’s clefts : a novel multi-functional organelle in the cytoplasm of Plasmodium falciparum-infected erythrocytes. Int. J. Parasitol. 36 : 23 – 36.

Vincensini, L., Fall G., Berry L., Blisnick T. and Braun Breton C. (2008). The RhopH complex is transferred to the host cell cytoplasm following red blood cell invasion by Plasmodium falciparum. Mol. Biochem. Parasitol. 160(2) : 81-89

Saridaki T., Frohlich K.S., Braun Breton C. and Lanzer M. (2009). Export of PfSBP1 to the Plasmodium falciparum Maurer’s clefts. Traffic.10(2) : 137-152

Lalle M, Curra C, Ciccarone F, Pace T, Cecchetti S, Fantozzi L, Ay B, Braun-Breton C, Ponzi M. (2010). Dematin, a component of the erythrocyte membrane-skeleton, is internalized by the malaria parasite and associates with Plasmodium 14-3-3. J. Biol. Chem. 286(2):1227-36

Abkarian, M., Massiera, G., Berry, L., Roques, M. and Braun-Breton, C. (2011). A novel mechanism for egress of malarial parasite from red blood cells. Blood 117(15):4118-24

Mbengue, A., Yam, X.Y. and Braun-Breton, C. (2012) Human erythrocyte remodelling during Plasmodium falciparum malaria parasite growth and egress. British J. Haematol. In press

Dans la même rubrique :

  • Catherine BRAUN-BRETON