Novel <i><scp>P</scp>lasmodium falciparum</i> <scp>M</scp>aurer's clefts protein families implicated in the release of infectious merozoites

The pathogenicity of the most deadly human malaria parasite, Plasmodium falciparum, relies on the export of virulence factors to the surface of infected erythrocytes. A novel membrane compartment, referred to as Maurer's clefts, is transposed to the host erythrocyte, acting as a marshal platform in the red blood cell cytoplasm, for exported parasite proteins addressed to the host cell plasma membrane. We report here the characterization of three new P. falciparum multigene families organized in 9 highly conserved clusters with the Pfmc-2tm genes in the subtelomeric regions of parasite's chromosomes and expressed at early trophozoite stages. Like the PfMC-2TM proteins, the PfEPF1, 3 and 4 proteins encoded by these families are exported to the Maurer's clefts, as peripheral or integral proteins of the Maurer's cleft membrane and largely exposed to the red cell cytosolic face of this membrane. A promoter titration approach was used to question the biological roles of these P. falciparum-specific exported proteins. Using the Pfepf1 family promoter, we observed the specific downregulation of all four families, correlating with the inefficient release of merozoites while the parasite intra-erythrocytic maturation and Maurer's clefts morphology were not impacted.