A gene-family encoding small exported proteins is conserved across Plasmodium genus

A gene-family, named sep, encoding small exported proteins conserved across Plasmodium species has been identified. SEP proteins (13–16 kDa) contain a predicted signal peptide at the NH 2-terminus, an internal hydrophobic region and a polymorphic, low-complexity region at the carboxy-terminus. One member of the Plasmodium berghei family, Pb sep1, encodes an integral membrane protein expressed along the entire erythrocytic cycle. Immunolocalisation results indicated that PbSEP1 is targeted to the membrane of the parasitophorous vacuole up to the early phases of schizogony, while, in late schizonts, it re-locates in structures within the syncitium. After erythrocyte rupture, PbSEP1 is still detectable in free merozoites thus suggesting its involvement in the early steps of parasite invasion. Seven members of the sep-family in Plasmodium falciparum have been identified. Two of them correspond to previously reported gene sequences included in a family of early transcribed membrane proteins ( etramp). Structural, functional and phylogenetic features of the sep family, shown in the present work, supercede this previous classification. PfSEP proteins are exported beyond the parasite membrane and translocated, early after invasion, to the host cell compartment in association with vesicle-like structures. Colocalisation results indicated that PfSEP-specific fluorescence overlaps, at the stage of trophozoite, with that of Pf332, a protein associated with Maurer’s clefts, membranous structures in the cytosol of parasitised red blood cells, most probably involved in trafficking of parasite proteins. The specific signals necessary to direct SEP proteins to the vacuolar membrane in P. berghei or to the host cell compartment in P. falciparum remain to be determined.