Abstract
Survival and virulence of the human malaria parasite Plasmodium falciparum during the blood stage of infection critically depend on extensive host cell refurbishments mediated through export of numerous parasite proteins into the host cell. The parasite-derived membranous structures called Maurer's clefts (MC) play an important role in protein trafficking from the parasite to the red blood cell membrane. However, their specific function has yet to be determined. We identified and characterized a new MC membrane protein, termed small exported membrane protein 1 (SEMP1). Upon invasion it is exported into the RBC cytosol where it inserts into the MCs before it is partly translocated to the RBC membrane. Using conventional and conditional loss-of-function approaches we showed that SEMP1 is not essential for parasite survival, gametocytogenesis, or PfEMP1 export under culture conditions. Co-IP experiments identified several potential interaction partners, including REX1 and other membrane-associated proteins that were confirmed to co-localize with SEMP1 at MCs. Transcriptome analysis further showed that expression of a number of exported parasite proteins was up-regulated in SEMP1-depleted parasites. By using Co-IP and transcriptome analysis for functional characterization of an exported parasite protein we provide a new starting point for further detailed dissection and characterisation of MC-associated protein complexes.
Highlights
The protozoan parasite Plasmodium falciparum causes the most severe form of human malaria responsible for nearly 7009000 deaths annually [1]
When parasite-lysates were probed with antibodies against 3xHA or green fluorescent protein (GFP), a protein of approximately 20 kDa and 40 kDa in size was observed in small exported membrane protein 1 (SEMP1)-3xHA and SEMP1-GFP transfectants (Fig 1B), respectively, and no signal was detected in uninfected red blood cell (RBC)
Maurer’s clefts (MC) have a crucial role in protein trafficking to the iRBC membrane and there is evidence that they act as secretory organelles concentrating virulence proteins destined for the host cell membrane [3,4], but further functions have yet to be determined
Summary
The protozoan parasite Plasmodium falciparum causes the most severe form of human malaria responsible for nearly 7009000 deaths annually [1]. Human RBCs are highly specialized cells devoid of all internal organelles survival of P. falciparum critically depends on extensive host cell refurbishments mediated by the export of parasite proteins into the RBC cytoplasm. This culminates in the insertion of the major parasite virulence factor PfEMP1 into the host cell membrane resulting in cell adhesion to receptors on endothelial cells. SEMP1 is a small PEXEL-negative protein, expressed early during blood stage infection, and exported to the MCs before being partially translocated further to the RBC membrane where it is suggested to be involved in membrane modification
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