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.
Highlights
Membrane trafficking pathways play critical roles in Apicomplexa, a phylum of protozoan parasites that cause life-threatening diseases worldwide
The retromer complex was first identified in yeast and mammals as a heteropentameric complex typified by a cargoselective complex that was built around the Vps35–Vps29–Vps[26] trimer and a dimer of different sorting nexins[28,35,36,37,38]
Our previous findings that TgSORTLR receptor is involved in the recruitment of Vps[26] and Vps[35] homologues prompted us to investigate how the retromer complex regulates retrograde transport as well as other functions in T. gondii
Summary
Membrane trafficking pathways play critical roles in Apicomplexa, a phylum of protozoan parasites that cause life-threatening diseases worldwide. T. gondii has common eukaryotic organelles, including the nucleus, endoplasmic reticulum and a single Golgi stack, and specific secretory organelles named dense granules, micronemes and rhoptries that contain parasite-derived factors required for host infection. The trafficking mechanisms employed by T. gondii retain several typical eukaryote components as well as evolving divergent features Protein trafficking of this parasite is mediated by entry into a canonical endoplasmic reticulum followed by vesicle packaging through a single Golgi complex[2,3]. The secretory pathway of T. gondii can be considered a strippeddown version of the more complex trafficking machinery that characterizes higher eukaryotes Despite this minimal trafficking machinery, the parasites actively rely on a membrane vesicle formation and transport during its intracellular lifecycle; to date, comparatively little is known about the mechanisms involved in trafficking pathways in T. gondii. The C-terminal tail of TgSORTLR was shown to be involved in recruiting many cytosolic cargo proteins including two homologues of the core retromer components, Vps[26] and Vps[35] (ref. 17), which are known to regulate retrograde transport from endosomes to the trans-Golgi network (TGN) in yeast and mammals[18,19]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
