title: Toxoplasma gondii Toc75 Functions in Import of Stromal but not Peripheral Apicoplast Proteins.
abstract: Apicomplexa are unicellular parasites causing important human and animal diseases, including malaria and toxoplasmosis. Most of these pathogens possess a relict but essential plastid, the apicoplast. The apicoplast was acquired by secondary endosymbiosis between a red alga and a flagellated eukaryotic protist. As a result the apicoplast is surrounded by four membranes. This complex structure necessitates a system of transport signals and translocons allowing nuclear encoded proteins to find their way to specific apicoplast sub-compartments. Previous studies identified translocons traversing two of the four apicoplast membranes. Here we provide functional support for the role of an apicomplexan Toc75 homolog in apicoplast protein transport. We identify two apicomplexan genes encoding Toc75 and Sam50, both members of the Omp85 protein family. We localize the respective proteins to the apicoplast and the mitochondrion of Toxoplasma and Plasmodium. We show that the Toxoplasma Toc75 is essential for parasite growth and that its depletion results in a rapid defect in the import of apicoplast stromal proteins while the import of proteins of the outer compartments is affected only as the secondary consequence of organelle loss. These observations along with the homology to Toc75 suggest a potential role in transport through the second innermost membrane.
authors.affiliation: Center for Tropical and Emerging Global Diseases & Department of Cellular Biology, University of Georgia, 500 D.W. Brooks Drive, Athens, GA, 30602, USA.|Wellcome Trust Centre For Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences, Sir Graeme Davies Building, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK.
authors.forename: Lilach
authors.initials: L
authors.lastname: Sheiner
authors.affiliation: Center for Tropical and Emerging Global Diseases & Department of Cellular Biology, University of Georgia, 500 D.W. Brooks Drive, Athens, GA, 30602, USA.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Fellows
authors.affiliation: Wellcome Trust Centre For Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences, Sir Graeme Davies Building, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK.
authors.forename: Jana
authors.initials: J
authors.lastname: Ovciarikova
authors.affiliation: Center for Tropical and Emerging Global Diseases & Department of Cellular Biology, University of Georgia, 500 D.W. Brooks Drive, Athens, GA, 30602, USA.
authors.forename: Carrie F
authors.initials: CF
authors.lastname: Brooks
authors.affiliation: Center for Tropical and Emerging Global Diseases & Department of Cellular Biology, University of Georgia, 500 D.W. Brooks Drive, Athens, GA, 30602, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Center for Tropical and Emerging Global Diseases & Department of Cellular Biology, University of Georgia, 500 D.W. Brooks Drive, Athens, GA, 30602, USA.
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Holmes
authors.affiliation: Department of Parasitology, Faculty of Biology, Philipps University Marburg, Marburg, Germany.
authors.forename: Irine
authors.initials: I
authors.lastname: Bietz
authors.affiliation: Molecular Cell Biology of Plants, Biocenter N200, 3. OG, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Flinner
authors.affiliation: Department of Parasitology, Faculty of Biology, Philipps University Marburg, Marburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Heiny
authors.affiliation: Molecular Cell Biology of Plants, Biocenter N200, 3. OG, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mirus
authors.affiliation: Department of Parasitology, Faculty of Biology, Philipps University Marburg, Marburg, Germany.
authors.forename: Jude M
authors.initials: JM
authors.lastname: Przyborski
authors.affiliation: Center for Tropical and Emerging Global Diseases & Department of Cellular Biology, University of Georgia, 500 D.W. Brooks Drive, Athens, GA, 30602, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Striepen
mesh_terms: D016782:Apicomplexa / Q000235:genetics / Q000378:metabolism; D063546:Apicoplasts / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D005347:Fibroblasts / Q000469:parasitology; D049452:Green Fluorescent Proteins; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000235:genetics; D010802:Phylogeny; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D010649:Phenylalanine
keywords: Omp85; Plasmodium; Sam50; Toc75; Toxoplasma; apicomplexa; apicoplast; complex plastid; protein trafficking