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

Lamba Omar Sangaré (1) , Tchilabalo Dilezitoko Alayi (2, 3) , Benoit Westermann (2) , Agnes Hovasse (2) , Fabien Sindikubwabo (4) , Isabelle Callebaut (5) , Elisabeth Werkmeister (6) , Frank Lafont (6) , Christian Slomianny (7) , Mohamed-Ali Hakimi (4) , Alain van Dorsselaer (2) , Christine Schaeffer-Reiss (2) , Stanislas Tomavo (1, 3)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 IPHC - Institut Pluridisciplinaire Hubert Curien
3 P3M - Protéomique et Peptides Modifiés - PLBS
4 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
5 IMPMC - Institut de minéralogie, de physique des matériaux et de cosmochimie
6 IBL - Institut de biologie de Lille - UMS 3702
7 PHYCELL - Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003

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.

Domaines: Sciences du Vivant [q-bio]

Lamba Omar Sangaré, Tchilabalo Dilezitoko Alayi, Benoit Westermann, Agnes Hovasse, Fabien Sindikubwabo, et al.. Unconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection. Nature Communications, 2016, 7, pp.11191. ⟨10.1038/ncomms11191⟩. ⟨hal-01310566⟩