{"gene":"TG_310460","gene_symbol":"RAB6","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2002,"finding":"T. gondii Rab6 localizes to cisternal rims of the late Golgi and trans-Golgi network, associated transport vesicles, and microdomains of dense granule and endosomal membranes, and regulates retrograde transport from post-Golgi dense granule organelles back to the Golgi and ER.","method":"Overexpression of wild-type and GTP-activated Rab6(Q70L) mutant causing rerouting of dense granule proteins to Golgi/ER; nucleotide-free Rab6(N124I) and GDP-bound Rab6(T25N) mutants causing accumulation of dense granule proteins in Golgi and reduced GRA4 secretion and delayed GRA2 glycosylation; colocalization with Golgi/dense granule markers.","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple dominant-active and dominant-negative mutants with distinct, consistent phenotypic readouts (protein mislocalization, secretion defects, glycosylation delay) in a single rigorous study.","pmids":["12468555"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2002,"finding":"Activated Rab6 on Golgi membranes colocalizes with centrin during mitosis, and parasites expressing Rab6 mutants show a partial shift in cytokinesis from endodyogeny (two daughter cells) to endopolygeny (multiple daughter cells), linking Rab6-regulated Golgi trafficking to parasite cell division.","method":"Colocalization of Rab6 with centrin by fluorescence microscopy; analysis of cytokinesis mode in parasite clones expressing Rab6 mutants.","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — colocalization and mutant phenotype from a single lab study; cytokinesis link is based on single-method observation without reconstitution.","pmids":["12468555"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"TgMyoF (an unconventional myosin motor) and F-actin control the directed transport of Rab6-positive vesicles, placing Rab6-positive vesicular trafficking under cytoskeletal regulation in the endomembrane system.","method":"Live imaging and functional analysis of TgMyoF perturbation showing loss of directed Rab6-positive vesicle movement; F-actin perturbation experiments.","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct imaging of Rab6-positive vesicle dynamics upon TgMyoF perturbation in a single lab study with functional consequences.","pmids":["33529198"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"TgGST2, a Golgi-endosomal membrane protein, colocalizes with Rab6 and other vesicle transport factors; loss of TgGST2 causes redistribution of Rab6 into discrete puncta and mislocalization of secretory proteins, indicating that TgGST2 is required for maintaining normal Rab6 compartment organization.","method":"Colocalization by fluorescence microscopy; knockout of TgGST2 followed by analysis of Rab6 distribution and secretory protein localization.","journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, colocalization plus KO phenotype, but the mechanistic link between TgGST2 and Rab6 function is indirect and not biochemically resolved.","pmids":["33543805"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"T. gondii Rab6 is a late Golgi/trans-Golgi network GTPase that mediates retrograde vesicular transport from post-Golgi dense granule organelles back to the Golgi and ER; its GTP/GDP cycle is required for correct dense granule protein secretion and glycosylation, its Golgi-associated pool colocalizes with centrin during mitosis and influences cytokinesis mode, and its vesicle dynamics are driven by the actin–TgMyoF cytoskeletal machinery."},"narrative":{"mechanistic_narrative":"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].","teleology":[{"year":2002,"claim":"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","pmids":["12468555"],"confidence":"High","gaps":["Downstream effectors, GEFs, and GAPs of the Rab6 GTP/GDP cycle not identified","Direct cargo-binding partners not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2002,"claim":"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","pmids":["12468555"],"confidence":"Medium","gaps":["Mechanistic basis of the endodyogeny-to-endopolygeny shift unresolved","Single-method colocalization without reconstitution"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"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","pmids":["33529198"],"confidence":"Medium","gaps":["Whether TgMyoF engages Rab6 vesicles directly or via adaptors is unknown","Cargo carried by the motile vesicle pool not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"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","pmids":["33543805"],"confidence":"Low","gaps":["Mechanistic link between TgGST2 and Rab6 is indirect and not biochemically resolved","No direct physical interaction demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The regulatory network of the Rab6 GTPase cycle — its GEFs, GAPs, effectors, and direct cargo/motor adaptors — remains uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No GEF or GAP identified","No direct effector or motor-adaptor interaction resolved biochemically"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["CENTRIN","TGMYOF","TGGST2"],"other_free_text":["Rab6-positive vesicle motility depends on F-actin and the unconventional myosin TgMyoF [#2].","Loss of the Golgi-endosomal protein TgGST2 causes Rab6 to redistribute into discrete puncta with secretory protein mislocalization [#3].","Rab6 GTP/GDP mutants perturb dense granule cargo routing, GRA4 secretion, and GRA2 glycosylation [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"12468555","id":"PMC_12468555","title":"Toxoplasma gondii Rab6 mediates a retrograde pathway for sorting of constitutively secreted proteins to the Golgi complex.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12468555","citation_count":33,"is_preprint":false},{"pmid":"33529198","id":"PMC_33529198","title":"Actin and an unconventional myosin motor, TgMyoF, control the organization and dynamics of the endomembrane network in Toxoplasma gondii.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33529198","citation_count":28,"is_preprint":false},{"pmid":"33543805","id":"PMC_33543805","title":"Toxoplasma gondii glutathione S-transferase 2 plays an important role in partial secretory protein transport.","date":"2021","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/33543805","citation_count":15,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3784,"output_tokens":1288,"usd":0.015336,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6277,"output_tokens":2485,"usd":0.046755,"stage2_stop_reason":"end_turn"},"total_usd":0.062091,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"T. gondii Rab6 localizes to cisternal rims of the late Golgi and trans-Golgi network, associated transport vesicles, and microdomains of dense granule and endosomal membranes, and regulates retrograde transport from post-Golgi dense granule organelles back to the Golgi and ER.\",\n      \"method\": \"Overexpression of wild-type and GTP-activated Rab6(Q70L) mutant causing rerouting of dense granule proteins to Golgi/ER; nucleotide-free Rab6(N124I) and GDP-bound Rab6(T25N) mutants causing accumulation of dense granule proteins in Golgi and reduced GRA4 secretion and delayed GRA2 glycosylation; colocalization with Golgi/dense granule markers.\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple dominant-active and dominant-negative mutants with distinct, consistent phenotypic readouts (protein mislocalization, secretion defects, glycosylation delay) in a single rigorous study.\",\n      \"pmids\": [\"12468555\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Activated Rab6 on Golgi membranes colocalizes with centrin during mitosis, and parasites expressing Rab6 mutants show a partial shift in cytokinesis from endodyogeny (two daughter cells) to endopolygeny (multiple daughter cells), linking Rab6-regulated Golgi trafficking to parasite cell division.\",\n      \"method\": \"Colocalization of Rab6 with centrin by fluorescence microscopy; analysis of cytokinesis mode in parasite clones expressing Rab6 mutants.\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — colocalization and mutant phenotype from a single lab study; cytokinesis link is based on single-method observation without reconstitution.\",\n      \"pmids\": [\"12468555\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TgMyoF (an unconventional myosin motor) and F-actin control the directed transport of Rab6-positive vesicles, placing Rab6-positive vesicular trafficking under cytoskeletal regulation in the endomembrane system.\",\n      \"method\": \"Live imaging and functional analysis of TgMyoF perturbation showing loss of directed Rab6-positive vesicle movement; F-actin perturbation experiments.\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging of Rab6-positive vesicle dynamics upon TgMyoF perturbation in a single lab study with functional consequences.\",\n      \"pmids\": [\"33529198\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TgGST2, a Golgi-endosomal membrane protein, colocalizes with Rab6 and other vesicle transport factors; loss of TgGST2 causes redistribution of Rab6 into discrete puncta and mislocalization of secretory proteins, indicating that TgGST2 is required for maintaining normal Rab6 compartment organization.\",\n      \"method\": \"Colocalization by fluorescence microscopy; knockout of TgGST2 followed by analysis of Rab6 distribution and secretory protein localization.\",\n      \"journal\": \"FASEB journal : official publication of the Federation of American Societies for Experimental Biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, colocalization plus KO phenotype, but the mechanistic link between TgGST2 and Rab6 function is indirect and not biochemically resolved.\",\n      \"pmids\": [\"33543805\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"T. gondii Rab6 is a late Golgi/trans-Golgi network GTPase that mediates retrograde vesicular transport from post-Golgi dense granule organelles back to the Golgi and ER; its GTP/GDP cycle is required for correct dense granule protein secretion and glycosylation, its Golgi-associated pool colocalizes with centrin during mitosis and influences cytokinesis mode, and its vesicle dynamics are driven by the actin–TgMyoF cytoskeletal machinery.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"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 [#0]. 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 [#0]. 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 [#1]. Directed movement of Rab6-positive vesicles is driven by the unconventional myosin TgMyoF and F-actin, placing this trafficking under cytoskeletal control [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"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.\",\n      \"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\",\n      \"pmids\": [\"12468555\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream effectors, GEFs, and GAPs of the Rab6 GTP/GDP cycle not identified\", \"Direct cargo-binding partners not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Linked Rab6-regulated Golgi trafficking to the parasite cell-division apparatus, addressing whether secretory trafficking intersects cytokinesis.\",\n      \"evidence\": \"Colocalization of activated Rab6 with centrin and cytokinesis-mode scoring in Rab6-mutant parasite clones in T. gondii\",\n      \"pmids\": [\"12468555\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic basis of the endodyogeny-to-endopolygeny shift unresolved\", \"Single-method colocalization without reconstitution\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Placed Rab6-positive vesicle transport under cytoskeletal control, answering how these vesicles achieve directed movement.\",\n      \"evidence\": \"Live imaging of Rab6-positive vesicle dynamics under TgMyoF and F-actin perturbation in T. gondii\",\n      \"pmids\": [\"33529198\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether TgMyoF engages Rab6 vesicles directly or via adaptors is unknown\", \"Cargo carried by the motile vesicle pool not defined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified TgGST2 as a factor required to maintain Rab6 compartment organization, probing what sustains the integrity of the Rab6 membrane domain.\",\n      \"evidence\": \"Colocalization and TgGST2 knockout with analysis of Rab6 redistribution into puncta and secretory protein mislocalization in T. gondii\",\n      \"pmids\": [\"33543805\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Mechanistic link between TgGST2 and Rab6 is indirect and not biochemically resolved\", \"No direct physical interaction demonstrated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The regulatory network of the Rab6 GTPase cycle — its GEFs, GAPs, effectors, and direct cargo/motor adaptors — remains uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No GEF or GAP identified\", \"No direct effector or motor-adaptor interaction resolved biochemically\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005525\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005802\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0030139\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006890\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0045045\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0000281\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"centrin\", \"TgMyoF\", \"TgGST2\"],\n    \"other_free_text\": [\n      \"Rab6-positive vesicle motility depends on F-actin and the unconventional myosin TgMyoF [#2].\",\n      \"Loss of the Golgi-endosomal protein TgGST2 causes Rab6 to redistribute into discrete puncta with secretory protein mislocalization [#3].\",\n      \"Rab6 GTP/GDP mutants perturb dense granule cargo routing, GRA4 secretion, and GRA2 glycosylation [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_310460","name":"RAB6","product":"ras-related protein RAB6","uniprot_acc":"A0A125YYB7","chromosome":"TGME49_chrXI","start_pos":1366768},{"strain":"GT1","gene_id":"TGGT1_310460","name":null,"product":"Rab6","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":1331540},{"strain":"RH88","gene_id":"TGRH88_050000","name":null,"product":"Rab6","uniprot_acc":null,"chromosome":"CM023092","start_pos":1417318},{"strain":"VEG","gene_id":"TGVEG_310460","name":null,"product":"Rab6","uniprot_acc":"A0A0F7V4D1","chromosome":"TGVEG_chrXI","start_pos":1380170}]}