Unconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection

• Published in: Nature communications Vol. 7; no. 1; p. 11191
• Main Authors: Sangaré, Lamba Omar, Alayi, Tchilabalo Dilezitoko, Westermann, Benoit, Hovasse, Agnes, Sindikubwabo, Fabien, Callebaut, Isabelle, Werkmeister, Elisabeth, Lafont, Frank, Slomianny, Christian, Hakimi, Mohamed-Ali, Van Dorsselaer, Alain, Schaeffer-Reiss, Christine, Tomavo, Stanislas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.04.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/19; 14/5; 631/250/255/1715; 631/326/417; 631/45/612/1237; 631/80/313; 82/58; 82/83; Amino Acid Sequence; Animals; Biosynthesis; Cell Compartmentation; Cell Membrane - metabolism; Endocytosis; Endoplasmic reticulum; Endosomes - metabolism; Gene Silencing; Genes, Protozoan; Host-Parasite Interactions; Humanities and Social Sciences; Infections; Life Sciences; Ligands; Molecular Sequence Data; multidisciplinary; Multiprotein Complexes - metabolism; Organelle Biogenesis; Parasites; Parasites - metabolism; Phenotype; Protein Interaction Mapping; Proteins; Protozoa; Protozoan Proteins - chemistry; Protozoan Proteins - metabolism; Science; Science (multidisciplinary); Species Specificity; Toxoplasma - genetics; Toxoplasma - metabolism; Vesicular Transport Proteins - metabolism; France
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11191

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 Tg Vps35 reveals that the retromer complex is crucial for the biogenesis of secretory organelles and for maintaining parasite morphology. We identify Tg HP12 as a parasite-specific and retromer-associated protein with functions unrelated to secretory organelle formation. Furthermore, the major facilitator superfamily homologue named Tg HP03, 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. The retromer complex is a multi-protein component of the endosomal protein sorting machinery. Here, Sangaré et al . identify unique features in the retromer complex of the parasite Toxoplasma gondii , and show that it is crucial for the biogenesis of secretory organelles in this pathogen.