title: Trafficking of STEVOR to the Maurer's clefts in Plasmodium falciparum-infected erythrocytes.
abstract: The human malarial parasite Plasmodium falciparum exports proteins to destinations within its host erythrocyte, including cytosol, surface and membranous profiles of parasite origin termed Maurer's clefts. Although several of these exported proteins are determinants of pathology and virulence, the mechanisms and trafficking signals underpinning protein export are largely uncharacterized-particularly for exported transmembrane proteins. Here, we have investigated the signals mediating trafficking of STEVOR, a family of transmembrane proteins located at the Maurer's clefts and believed to play a role in antigenic variation. Our data show that, apart from a signal sequence, a minimum of two addition signals are required. This includes a host cell targeting signal for export to the host erythrocyte and a transmembrane domain for final sorting to Maurer's clefts. Biochemical studies indicate that STEVOR traverses the secretory pathway as an integral membrane protein. Our data suggest general principles for transport of transmembrane proteins to the Maurer's clefts and provide new insights into protein sorting and trafficking processes in P. falciparum.
authors.affiliation: Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Jude M
authors.initials: JM
authors.lastname: Przyborski
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Miller
authors.forename: Judith M
authors.initials: JM
authors.lastname: Pfahler
authors.forename: Philipp P
authors.initials: PP
authors.lastname: Henrich
authors.forename: Petra
authors.initials: P
authors.lastname: Rohrbach
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Michael
authors.initials: M
authors.lastname: Lanzer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006790:Host-Parasite Interactions; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010963:Plasmodium falciparum / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; C474556:STEVOR antigen, Plasmodium falciparum; D049452:Green Fluorescent Proteins