VPS11

TgVps11 is a core subunit of the HOPS and CORVET vesicle-tethering complexes in Toxoplasma gondii, forming part of the conserved Vps-C core that mediates vesicle tethering and fusion within the endosomal pathway (PMID:25640905). It localizes dynamically to Golgi endosomal-related compartments, the parasitophorous vacuole, and immature apical secretory organelles (PMID:25640905). Conditional knock-down establishes that TgVps11 is essential for the biogenesis and proper localization of all three apical secretory organelle types — dense granules, rhoptries, and micronemes — with downstream loss of parasite motility, host cell invasion, egress, and intracellular growth (PMID:25640905). Beyond these findings, no further mechanistic detail has been characterized in the available corpus.

1. 2015 Medium

   It was unknown whether the conserved Vps-C tethering machinery operates in apicomplexan parasites; identifying TgVps11 as a HOPS/CORVET subunit established that T. gondii uses this endosomal tethering core.

   Evidence Ortholog identification and functional characterization in T. gondii

   PMID:25640905

   Open questions at the time

   • Direct biochemical demonstration of HOPS/CORVET complex assembly and interaction partners not established
   • Molecular tethering/fusion activity not reconstituted
2. 2015 Medium

   Where TgVps11 acts within the parasite was unresolved; direct imaging placed it at Golgi endosomal compartments, the parasitophorous vacuole, and immature secretory organelles, linking it spatially to the secretory pathway.

   Evidence Fluorescence microscopy of tagged protein in T. gondii

   PMID:25640905

   Open questions at the time

   • Dynamics of compartment transitions not resolved at high temporal resolution
   • Whether localization reflects HOPS versus CORVET function not distinguished
3. 2015 High

   The functional requirement for endosomal tethering in organelle biogenesis was unknown; conditional knock-down showed TgVps11 is essential for biogenesis of dense granules, rhoptries, and micronemes, and consequently for motility, invasion, egress, and replication.

   Evidence Conditional knock-down with phenotypic readouts for organelle biogenesis, motility, invasion, and egress, internally replicated across HOPS complex subunits

   PMID:25640905

   Open questions at the time

   • Molecular cargo/machinery routed through TgVps11-dependent tethering to each organelle not identified
   • Whether the three organelle biogenesis defects share one common upstream step or diverge is unresolved

• The biochemical composition, cargo specificity, and mechanism by which TgVps11-containing complexes drive apical organelle biogenesis remain undefined.
• No reconstitution of HOPS/CORVET tethering activity
• No identified substrate or cargo
• No structural model of the complex