RAB6

Toxoplasma gondii Rab6 is a late Golgi/trans-Golgi network GTPase that governs retrograde vesicular transport from post-Golgi dense granule organelles back to the Golgi and ER, thereby ensuring correct dense granule protein secretion and glycosylation (PMID:12468555). It localizes to the cisternal rims of the late Golgi and TGN, associated transport vesicles, and microdomains of dense granule and endosomal membranes, and cycles between GTP- and GDP-bound states: GTP-activated Rab6(Q70L) reroutes dense granule proteins to the Golgi/ER, while nucleotide-free and GDP-locked mutants trap these proteins in the Golgi, reduce GRA4 secretion, and delay GRA2 glycosylation (PMID:12468555). The Golgi-associated activated pool colocalizes with centrin during mitosis, and Rab6 mutants partially shift parasite division from endodyogeny toward endopolygeny, coupling Rab6-regulated trafficking to cytokinesis (PMID:12468555). Directed movement of Rab6-positive vesicles is driven by the unconventional myosin TgMyoF and F-actin, placing this trafficking under cytoskeletal control (PMID:33529198).

1. 2002 High

   Established that Rab6 defines a late Golgi/TGN GTPase controlling retrograde traffic from dense granule organelles, resolving how post-Golgi secretory cargo is routed and processed.

   Evidence Overexpression of GTP-locked (Q70L), nucleotide-free (N124I), and GDP-bound (T25N) Rab6 mutants with cargo mislocalization, GRA4 secretion, and GRA2 glycosylation readouts, plus marker colocalization in T. gondii

   PMID:12468555

   Open questions at the time

   • Downstream effectors, GEFs, and GAPs of the Rab6 GTP/GDP cycle not identified
   • Direct cargo-binding partners not resolved
2. 2002 Medium

   Linked Rab6-regulated Golgi trafficking to the parasite cell-division apparatus, addressing whether secretory trafficking intersects cytokinesis.

   Evidence Colocalization of activated Rab6 with centrin and cytokinesis-mode scoring in Rab6-mutant parasite clones in T. gondii

   PMID:12468555

   Open questions at the time

   • Mechanistic basis of the endodyogeny-to-endopolygeny shift unresolved
   • Single-method colocalization without reconstitution
3. 2021 Medium

   Placed Rab6-positive vesicle transport under cytoskeletal control, answering how these vesicles achieve directed movement.

   Evidence Live imaging of Rab6-positive vesicle dynamics under TgMyoF and F-actin perturbation in T. gondii

   PMID:33529198

   Open questions at the time

   • Whether TgMyoF engages Rab6 vesicles directly or via adaptors is unknown
   • Cargo carried by the motile vesicle pool not defined
4. 2021 Low

   Identified TgGST2 as a factor required to maintain Rab6 compartment organization, probing what sustains the integrity of the Rab6 membrane domain.

   Evidence Colocalization and TgGST2 knockout with analysis of Rab6 redistribution into puncta and secretory protein mislocalization in T. gondii

   PMID:33543805

   Open questions at the time

   • Mechanistic link between TgGST2 and Rab6 is indirect and not biochemically resolved
   • No direct physical interaction demonstrated

• The regulatory network of the Rab6 GTPase cycle — its GEFs, GAPs, effectors, and direct cargo/motor adaptors — remains uncharacterized in the available corpus.
• No GEF or GAP identified
• No direct effector or motor-adaptor interaction resolved biochemically