Malaria parasite proteins that remodel the host erythrocyte

Abstract

Exported proteins of the malaria parasite Plasmodium falciparum interact with proteins of the erythrocyte membrane and induce substantial changes in the morphology, physiology and function of the host cell. These changes underlie the pathology that is responsible for the deaths of 1-2 million children every year due to malaria infections. The advent of molecular transfection technology, including the ability to generate deletion mutants and to introduce fluorescent reporter proteins that track the locations and dynamics of parasite proteins, has increased our understanding of the processes and machinery for export of proteins in P. falciparum-infected erythrocytes and has provided us with insights into the functions of the parasite protein exportome. We review these developments, focusing on parasite proteins that interact with the erythrocyte membrane skeleton or that promote delivery of the major virulence protein, PfEMP1, to the erythrocyte membrane.

Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions

“…Parasite induced vesicu lar structures in the host cell termed 'Maurer's clefts' are believed to serve as platforms for the trafficking of P. falciparum proteins to the host cell surface 14 . Maurer's clefts can be detected from the late ring stage onwards 5,15 and are thought to originate through budding from the PVM or from extensions of the PVM termed the tubove sicular network, their number increasing as the parasite progresses through the cycle 2,[16][17][18][19][20] . This forms the basis for one model that could solve a mechanistic problem in protein export in malaria parasites: although soluble proteins can pass through the recently described translocon at the PVM 21 , it was proposed that transmembrane pro teins are loaded into nascent Maurer's clefts forming at the PVM and are thereby exported with the new cleft 2,17,18,22,23 .…”

“…Within the erythrocyte, the parasite develops in its own compartment formed by the parasitophorous vacuolar membrane (PVM). To thrive in this niche, the parasite extensively modifies the host cell through the export of a large number of proteins 2 .…”

Signalling in malaria parasites – The MALSIG consortium

“…Both classical and non-classical secretory pathways operate in P. falciparum-infected erythrocytes. Peptide motifs have now been identified within a large number of secreted proteins that direct their targeting to the red blood cell cytosol, the apicoplast and the food vacuole (Maier et al, 2009). In addition, motifs that direct proteins to rhoptries have recently been described (Richard et al, 2009), but in contrast the motifs necessary for targeting to micronemes have yet to be defined.…”

Flow cytometry as a tool for analyzing changes in Plasmodium falciparum cell cycle following treatment with indol compounds

“…Its asexual replicative cycle inside red blood cell (RBC) is responsible for pathogenesis and induces several structural and biochemical changes within the host cell (1,2). One striking feature regarding P. falciparum infection is associated with 48-h fever peaks intervals, as a result of from synchronous release of merozoites into the blood stream (3).…”