title: Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte.
abstract: The intracellular survival of Plasmodium falciparum within human erythrocytes is dependent on export of parasite proteins that remodel the host cell. Most exported proteins require a conserved motif (RxLxE/Q/D), termed the Plasmodium export element (PEXEL) or vacuolar targeting sequence (VTS), for targeting beyond the parasitophorous vacuole membrane and into the host cell; however, the precise role of this motif in export is poorly defined. We used transgenic P. falciparum expressing chimeric proteins to investigate the function of the PEXEL motif for export. The PEXEL constitutes a bifunctional export motif comprising a protease recognition sequence that is cleaved, in the endoplasmic reticulum, from proteins destined for export, in a PEXEL arginine- and leucine-dependent manner. Following processing, the remaining conserved PEXEL residue is required to direct the mature protein to the host cell. Furthermore, we demonstrate that N acetylation of proteins following N-terminal processing is a PEXEL-independent process that is insufficient for correct export to the host cell. This work defines the role of each residue in the PEXEL for export into the P. falciparum-infected erythrocyte.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Melbourne, Australia.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Boddey
authors.forename: Robert L
authors.initials: RL
authors.lastname: Moritz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins