Maurer’s cleft–associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells

Asexual stages of the malaria parasite Plasmodium falciparum invade and replicate in human RBCs. During the 48 h of its asexual life cycle, the parasite dramatically remodels the host RBC (for reviews see Cooke et al., 2001, 2004). This includes the generation of unique, fl attened membranous structures in the cytoplasm of the infected RBC (IRBC) called Maurer’s clefts and protrusions on the IRBC surface termed knobs. P. falciparum also exports several proteins into the host RBC by a mechanism that depends on the presence of an NH2-terminal motif, termed either the Plasmodium export element (PEXEL) or vacuolar transport signal (VTS), which is conserved across the Plasmodium genus (Hiller et al., 2004; Marti et al., 2004). One of the most important of these exported proteins is PfEMP1 (P. falciparum erythrocyte membrane protein 1), a protein of parasite origin that is exposed on the surface of IRBCs and mediates adhesion to several receptors expressed on the surface of vascular endothelial cells (Baruch et al., 2002). Ultimately, this results in the adhesion of mature parasite-infected RBCs to the vascular endothelium, which is a process that underpins the development of severe and often fatal complications that accompany P. falciparum malaria infection in humans (MacPherson et al., 1985; Pongponratn et al., 1991). Therefore, understanding the pathways and molecular mechanisms by which parasites export proteins to the RBC membrane is critical for a complete understanding of the pathogenesis of P. falciparum malaria and, in the longer term, could lead to the development of novel therapeutic approaches to prevent cytoadherence and severe pathological sequelae. For most parasite proteins that are destined for the RBC membrane skeleton and the surface, traffi cking seems to involve Maurer’s clefts (Przyborski et al., 2003; Marti et al., 2004; 10.1083/jcb.200509122200509122A Maurer’s cleft–associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells