title: A conditional export system provides new insights into protein export in Plasmodium falciparum-infected erythrocytes.
abstract: The human malarial parasite Plasmodium falciparum exports determinants of virulence and pathology to destinations within its host erythrocyte, including the cytoplasm, the plasma membrane and membrane profiles of parasite origin termed Maurer's clefts. While there is some information regarding the signals that allot proteins for export, the trafficking route itself has remained largely obscure, partly due to technical limitations in following protein trafficking with time. To overcome these shortcomings, we have established a conditional protein export system in P. falciparum, based on the previously described conditional aggregation domain (CAD domain) that self-aggregates in the endoplasmic reticulum in a manner that is reversible by the addition of a small molecule. By fusing the CAD domain to the first 80 amino acids of STEVOR and full-length PfSBP1, we were able to control export of a soluble and a transmembrane protein to the erythrocyte cytosol and the Maurer's clefts respectively. The conditional export system allowed us to study the temporal sequence of events of protein export and identify intermediate steps. We further explored the potential of the conditional export system in identifying factors that interact with exported proteins en route. Our data provide evidence for a physical interaction of exported proteins with the molecular chaperone PfBiP during early export steps.
authors.affiliation: Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: Theodora
authors.initials: T
authors.lastname: Saridaki
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Sanchez
authors.forename: Judith
authors.initials: J
authors.lastname: Pfahler
authors.forename: Michael
authors.initials: M
authors.lastname: Lanzer
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D017930:Genes, Reporter; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C474556:STEVOR antigen, Plasmodium falciparum