title: Unconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection.
abstract: Membrane trafficking pathways play critical roles in Apicomplexa, a phylum of protozoan parasites that cause life-threatening diseases worldwide. Here we report the first retromer-trafficking interactome in Toxoplasma gondii. This retromer complex includes a trimer Vps35-Vps26-Vps29 core complex that serves as a hub for the endosome-like compartment and parasite-specific proteins. Conditional ablation of TgVps35 reveals that the retromer complex is crucial for the biogenesis of secretory organelles and for maintaining parasite morphology. We identify TgHP12 as a parasite-specific and retromer-associated protein with functions unrelated to secretory organelle formation. Furthermore, the major facilitator superfamily homologue named TgHP03, which is a multiple spanning and ligand transmembrane transporter, is maintained at the parasite membrane by retromer-mediated endocytic recycling. Thus, our findings highlight that both evolutionarily conserved and unconventional proteins act in concert in T. gondii by controlling retrograde transport that is essential for parasite integrity and host infection.
authors.affiliation: Center for Infection and Immunity of Lille, INSERM U 1019, CNRS UMR 8204, Institut Pasteur de Lille, Université de Lille, 59000 Lille, France.
authors.forename: Lamba Omar
authors.initials: LO
authors.lastname: Sangaré
authors.affiliation: Laboratory of Bio-Organic Mass Spectrometry, IPHC, CNRS UMR 7178, Université de Strasbourg, 67087 Strasbourg, France.|Plateforme de Protéomique et des Peptides Modifiés (P3M), Institut Pasteur de Lille, CNRS, Université de Lille, 59000 Lille, France.
authors.forename: Tchilabalo Dilezitoko
authors.initials: TD
authors.lastname: Alayi
authors.affiliation: Laboratory of Bio-Organic Mass Spectrometry, IPHC, CNRS UMR 7178, Université de Strasbourg, 67087 Strasbourg, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Westermann
authors.affiliation: Laboratory of Bio-Organic Mass Spectrometry, IPHC, CNRS UMR 7178, Université de Strasbourg, 67087 Strasbourg, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hovasse
authors.affiliation: CNRS UMR5163, LAPM, Université Joseph Fourier, Grenoble 38000, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Sindikubwabo
authors.affiliation: CNRS UMR7590, Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, MNHN, IRD-IUC, Paris 75005, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.affiliation: Bioimaging Platform, IBL, CNRS, Université de Lille, 59000 Lille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Werkmeister
authors.affiliation: Bioimaging Platform, IBL, CNRS, Université de Lille, 59000 Lille, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Lafont
authors.affiliation: Laboratory of Cell Physiology, INSERM U 1003, Université de Lille, 59655 Villeneuve d'Ascq, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.affiliation: CNRS UMR5163, LAPM, Université Joseph Fourier, Grenoble 38000, France.
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
authors.affiliation: Laboratory of Bio-Organic Mass Spectrometry, IPHC, CNRS UMR 7178, Université de Strasbourg, 67087 Strasbourg, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.affiliation: Laboratory of Bio-Organic Mass Spectrometry, IPHC, CNRS UMR 7178, Université de Strasbourg, 67087 Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Schaeffer-Reiss
authors.affiliation: Center for Infection and Immunity of Lille, INSERM U 1019, CNRS UMR 8204, Institut Pasteur de Lille, Université de Lille, 59000 Lille, France.|Plateforme de Protéomique et des Peptides Modifiés (P3M), Institut Pasteur de Lille, CNRS, Université de Lille, 59000 Lille, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Tomavo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D020868:Gene Silencing; D017125:Genes, Protozoan; D006790:Host-Parasite Interactions; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D001678:Organelle Biogenesis; D010271:Parasites / Q000378:metabolism*; D010641:Phenotype; D025941:Protein Interaction Mapping; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D013045:Species Specificity; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D015800:Protozoan Proteins; D033921:Vesicular Transport Proteins