title: The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum.
abstract: During the blood stage of its lifecycle, the malaria parasite resides and replicates inside a membrane vacuole within its host cell, the human erythrocyte. The parasite exports many proteins across the vacuole membrane and into the host cell cytoplasm. Most exported proteins are characterized by the presence of a host targeting (HT) motif, also referred to as a Plasmodium export element (PEXEL), which corresponds to the consensus sequence RxLxE/D/Q. During export the HT motif is cleaved by an unknown protease. Here, we generate parasite lines expressing HT motif containing proteins that are localized to different compartments within the parasite or host cell. We find that the HT motif in a protein that is retained in the parasite endoplasmic reticulum is cleaved and N-acetylated as efficiently as a protein that is exported. This shows that cleavage of the HT motif occurs early in the secretory pathway, in the parasite endoplasmic reticulum.
authors.affiliation: Center for Rare and Neglected Diseases, University of Notre Dame, 103 Galvin Life Sciences, South Bend, IN 46556, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Osborne
authors.forename: Kaye D
authors.initials: KD
authors.lastname: Speicher
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Tamez
authors.forename: Souvik
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: David W
authors.initials: DW
authors.lastname: Speicher
authors.forename: Kasturi
authors.initials: K
authors.lastname: Haldar
mesh_terms: D000107:Acetylation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D010961:Plasmodium / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D021382:Protein Sorting Signals; D015800:Protozoan Proteins