Targeted mutagenesis of the ring-exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles.

Mature red blood cells have no internal trafficking machinery, so the intraerythrocytic malaria parasite, Plasmodium falciparum, establishes its own transport system to export virulence factors to the red blood cell surface. Maurer's clefts are parasite-derived membranous structures that form an important component of this exported secretory system. A protein with sequence similarity to a Golgi tethering protein, referred to as ring-exported protein-1 (REX1), is associated with Maurer's clefts. A REX1-GFP chimera is trafficked to the Maurer's clefts and preferentially associates with the edges of these structures, as well as with vesicle-like structures and with stalk-like extensions that are involved in tethering the Maurer's clefts to other membranes. We have generated transfected P. falciparum expressing REX1 truncations or deletion. Electron microscopy reveals that the Maurer's clefts of REX1 truncation mutants have stacked cisternae, while the 3D7 parent line has unstacked Maurer's clefts. D10 parasites, which have lost the right end of chromosome 9, including the rex1 gene, also display Maurer's clefts with stacked cisternae. Expression of full-length REX1-GFP in D10 parasites restores the 3D7-type unstacked Maurer's cleft phenotype. These studies reveal the importance of the REX1 protein in determining the ultrastructure of the Maurer's cleft system.