RON10

RON10 is a rhoptry neck protein of Toxoplasma gondii that partners with RON9 to form a high-molecular-mass complex distinct from the moving junction complex (RON2/4/5/8) and not detectable at the moving junction during invasion (PMID:22427839). RON9 and RON10 are mutually dependent: disruption of either protein causes retention of its partner in the ER and subsequent degradation, establishing that complex formation is required for ER exit and proper sorting to the rhoptries (PMID:22427839). Loss of the RON9/RON10 complex has no significant effect on rhoptry morphology, host cell invasion, parasite growth in fibroblasts, or virulence in mice, indicating that the complex is dispensable for the canonical lytic cycle in vitro (PMID:22427839). Beyond these findings, no further mechanistic role for RON10 has been characterized in the available corpus.

1. 2012 High

   Establishing that RON10 resides in the rhoptry neck as part of a discrete RON9/RON10 complex separated the protein from the known moving junction machinery and defined a new rhoptry neck sub-complex.

   Evidence Biochemical fractionation, reciprocal co-immunoprecipitation, and immunofluorescence/immunoelectron microscopy in Toxoplasma gondii

   PMID:22427839

   Open questions at the time

   • No molecular function or enzymatic/binding activity assigned to RON10 itself
   • Stoichiometry and additional members of the complex not defined
   • Reason the complex is excluded from the moving junction unresolved
2. 2012 High

   Knockout of either partner revealed a mutual dependency for ER exit and rhoptry targeting, showing that RON9/RON10 complex assembly is a prerequisite for proper trafficking rather than the proteins being independently sorted.

   Evidence Gene disruption of RON9 or RON10 with immunofluorescence and Western blot readouts of localization and stability in Toxoplasma gondii

   PMID:22427839

   Open questions at the time

   • Molecular basis of the ER-retention/degradation of the orphaned partner unknown
   • Trafficking machinery mediating rhoptry sorting of the complex not identified
3. 2012 Medium

   Phenotyping the knockouts showed the complex is dispensable for invasion, growth, and virulence in standard models, narrowing its likely functional relevance to contexts not captured by fibroblast infection or acute mouse virulence.

   Evidence Invasion and growth assays plus a mouse virulence model on RON9/RON10 knockouts in Toxoplasma gondii

   PMID:22427839

   Open questions at the time

   • Negative result from a single lab/single study
   • No functional assay in intestinal epithelial or developmental (sexual/enteric) stages where a role is hypothesized
   • No condition identified in which loss of the complex produces a phenotype

• The biological process in which the RON9/RON10 complex actually functions, and RON10's molecular activity within it, remain undefined.
• No stage- or tissue-specific phenotype demonstrated for the complex
• No molecular function or interaction beyond RON9 established for RON10
• No structural or mechanistic model of complex assembly or trafficking