RAB5C

In Toxoplasma gondii, RAB5C is a Rab-GTPase that regulates vesicular trafficking toward the apical secretory organelles, the micronemes and rhoptries; overexpression of a dominant-negative Rab5C disrupts targeting to these organelles, though only a subset of microneme protein trafficking depends on functional Rab5C, revealing that redundant microneme-targeting routes operate in parallel (PMID:23505371). Rab5C acts within an endosome-like sorting compartment that directs cargo to the secretory organelles, and it functions in a pathway that also involves the HOPS/CORVET tethering subunit TgVps11 (PMID:25640905). Beyond this role in endosome-to-secretory-organelle trafficking, no further mechanistic detail — including direct effectors, nucleotide-cycling regulators, or structural features — has been characterized in the available corpus.

1. 2013 Medium

   Establishing which Rab-GTPases govern biogenesis of the apical secretory organelles was open; a dominant-negative screen showed Rab5C is required for trafficking to micronemes and rhoptries yet dispensable for a subset of microneme cargo, defining it as one of several redundant targeting routes.

   Evidence Overexpression of dominant-negative Rab-GTPase constructs with two-colour super-resolution STED microscopy in T. gondii

   PMID:23505371

   Open questions at the time

   • The identity of the redundant, Rab5C-independent microneme-targeting pathway is not defined
   • No direct Rab5C effectors or GEF/GAP regulators identified
   • Dominant-negative overexpression does not exclude off-target dominance effects
2. 2015 Low

   Whether Rab5C connects to the endosomal tethering machinery was unresolved; conditional knockdown of the HOPS/CORVET subunit TgVps11 placed it in the same endosome-like sorting pathway that routes cargo to secretory organelles, positioning Rab5C upstream of or alongside tethering complexes.

   Evidence Conditional knockdown of TgVps11 with localization studies, referencing Rab5C as a prior pathway component (no direct Rab5C experiment)

   PMID:25640905

   Open questions at the time

   • No direct experiment on Rab5C was performed in this study; the pathway link is inferential
   • The order of action between Rab5C and the HOPS/CORVET complex is not established
   • Physical interaction between Rab5C and TgVps11 is not demonstrated

• The direct effectors, nucleotide-cycling regulators (GEFs/GAPs), and cargo-recognition mechanism of Rab5C in secretory-organelle biogenesis remain undefined.
• No effector or regulator of Rab5C identified
• No structural or biochemical characterization of Rab5C
• The redundant microneme-targeting pathway is uncharacterized