Thème 3 - Catherine Braun-Breton

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Theme 3:  Remodelling of the host cell by Plasmodium falciparum blood stages


Our research focuses on P. falciparum-induced changes of its host erythrocyte. Our main objectives are to decipher the roles of Maurer’s clefts, a membrane compartment transposed by the parasite at the periphery of its host cell and to characterize the parasite-induced changes of the erythrocyte membrane and cytoskeleton crucial for parasite entry into and egress from the red blood cell.
Axes de recherche

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.

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.

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Catherine BRAUN-BRETON
Professeur UM
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LPHI  Laboratory of Pathogen Host Interactions
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