{"gene":"TG_320480","gene_symbol":"RAB11B","run_date":"2026-09-08T15:15:14","timeline":{"discoveries":[{"year":2010,"finding":"TgRab11B is an alveolate-specific small GTPase that localizes to the growing end of the inner membrane complex (IMC) during replication of Toxoplasma gondii. Conditional interference with Rab11B function causes a profound defect in IMC biogenesis, demonstrating that Rab11B is required for transport of Golgi-derived vesicles to the nascent IMC of daughter cells. Notably, blocking IMC biogenesis via Rab11B did not affect formation of sub-pellicular microtubules, indicating these two processes are not mechanistically linked.","method":"Conditional dominant-negative/interference with Rab11B function; fluorescence localization; genetic epistasis with sub-pellicular microtubule formation","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional loss-of-function with defined cellular phenotype (IMC biogenesis defect) and direct localization, single lab but multiple orthogonal methods","pmids":["20686666"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"Localization of the F-box protein TgFBXO1 to the daughter cell scaffold during Toxoplasma replication is dependent on TgRab11B, placing TgRab11B upstream of TgFBXO1 in the vesicular trafficking pathway required for daughter cell scaffold and IMC formation.","method":"Genetic epistasis; conditional interference with TgRab11B; fluorescence localization of TgFBXO1 in Rab11B-depleted parasites","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — epistasis/localization experiment in single lab showing Rab11B dependency of TgFBXO1 scaffold localization, single method for this specific finding","pmids":["31348812"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Host cell Rab11B-positive recycling endosomal vesicles are selectively sequestered into the Toxoplasma parasitophorous vacuole (PV). The intra-PV delivery of vesicles bearing class I Rab11-FIPs (FIP1C, FIP2, FIP5) is dependent on Rab11 (including Rab11B) binding, whereas class II FIPs also use Arf6. Cell depletion of Rab11A (a close paralog) selectively reduces intra-PV FIP5 but not FIP3 vesicles, indicating specificity in the host Rab11 vesicle scavenging process.","method":"Quantitative fluorescence microscopy; host cell Rab11A/B depletion; FIP mutants abolishing Rab11/Arf6 binding; co-localization analysis of intra-PV vesicles","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal approaches (depletion, binding-mutants, quantitative microscopy) in single lab; finding concerns host Rab11B interaction with Toxoplasma PV","pmids":["35274991"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"TBC9, an essential TBC-domain Rab GTPase Activating Protein in Toxoplasma gondii, physically interacts with Rab11B (as well as Rab11A and Rab2) by pull-down assay, linking TBC9 to the Rab11B-dependent pathway for daughter IMC formation and early vesicular transport.","method":"Pull-down assay; conditional knockdown of TBC9 with phenotypic analysis of IMC formation and vesicular transport","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pull-down interaction plus functional epistasis context; single lab; direct interaction with Rab11B established by pull-down but full mechanistic detail on Rab11B itself is indirect","pmids":["38762629"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgRab11B is an alveolate-specific small GTPase that mediates vesicular transport from the Golgi to the nascent inner membrane complex (IMC) of daughter cells during Toxoplasma replication; it acts upstream of scaffold effectors such as TgFBXO1, is regulated by the TBC-domain GAP TBC9, and independently of this endogenous role, host Rab11B-positive recycling vesicles are selectively scavenged into the Toxoplasma parasitophorous vacuole via a Rab11-FIP-dependent mechanism."},"narrative":{"mechanistic_narrative":"TgRab11B is an alveolate-specific small GTPase that mediates vesicular transport from the Golgi to the nascent inner membrane complex (IMC) of daughter cells during Toxoplasma gondii replication; conditional interference with its function causes a profound IMC biogenesis defect without affecting sub-pellicular microtubule formation, establishing these as mechanistically separable processes [PMID:20686666]. TgRab11B acts upstream of the F-box scaffold protein TgFBXO1, whose recruitment to the daughter cell scaffold depends on TgRab11B function [PMID:31348812], and it is a substrate of the essential TBC-domain Rab GAP TBC9, which physically binds TgRab11B and links it to early vesicular transport and daughter IMC formation [PMID:38762629]. Independently of this endogenous replicative role, host-cell Rab11B-positive recycling endosomal vesicles are selectively scavenged into the Toxoplasma parasitophorous vacuole through a Rab11-FIP-dependent mechanism, with class I FIP delivery requiring Rab11 binding [PMID:35274991].","teleology":[{"year":2010,"claim":"Established that TgRab11B is required for building the daughter cell inner membrane complex, answering how Golgi-derived vesicles reach the nascent pellicle during endodyogeny and showing that IMC membrane biogenesis is uncoupled from cytoskeletal microtubule formation.","evidence":"Conditional dominant-negative interference with fluorescence localization and genetic epistasis against sub-pellicular microtubule formation in T. gondii","pmids":["20686666"],"confidence":"High","gaps":["Direct effectors and vesicle cargo transported by Rab11B not identified","GEF/GAP regulators of the GTPase cycle not defined at this stage","Molecular basis for targeting to the growing IMC end unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Placed TgRab11B upstream of the scaffold F-box protein TgFBXO1, connecting the GTPase-driven trafficking step to a defined downstream effector required for daughter scaffold and IMC assembly.","evidence":"Genetic epistasis with conditional TgRab11B interference and fluorescence localization of TgFBXO1 in Rab11B-depleted parasites","pmids":["31348812"],"confidence":"Medium","gaps":["Whether TgFBXO1 is a direct Rab11B effector or acts through intermediaries is unresolved","Single method for this specific epistasis finding"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Revealed a distinct host-directed role by showing host Rab11B recycling vesicles are selectively sequestered into the parasitophorous vacuole via a Rab11-FIP-dependent mechanism, defining specificity in parasite scavenging of host endosomal traffic.","evidence":"Quantitative fluorescence microscopy with host Rab11A/B depletion, FIP binding mutants, and co-localization of intra-PV vesicles","pmids":["35274991"],"confidence":"Medium","gaps":["Parasite factor(s) that recruit host Rab11B/FIP vesicles to the PV not identified","Functional consequence of host vesicle scavenging for the parasite not established","This role is distinct from the endogenous TgRab11B function and their relationship is not integrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Identified the essential TBC-domain GAP TBC9 as a physical interactor of TgRab11B, providing a candidate regulator of the GTPase cycle governing daughter IMC formation and early vesicular transport.","evidence":"Pull-down assay and conditional TBC9 knockdown with phenotypic analysis of IMC formation and vesicular transport in T. gondii","pmids":["38762629"],"confidence":"Medium","gaps":["TBC9 GAP activity toward Rab11B not demonstrated biochemically","TBC9 also binds Rab11A and Rab2, so Rab11B-specific regulation is not isolated","No structural detail of the interaction"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The GEF that activates TgRab11B, the direct effector repertoire beyond TgFBXO1, and the parasite factors mediating host Rab11B vesicle scavenging remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No GEF identified for the GTPase activation cycle","Direct vesicle cargo and tether proteins unknown","Mechanistic link between endogenous and host-scavenging roles unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGFBXO1 (DOWNSTREAM SCAFFOLD EFFECTOR, RAB11B-DEPENDENT LOCALIZATION)","TBC9 (TBC-DOMAIN RAB GAP, PHYSICAL INTERACTOR)","RAB11-FIPS FIP1C/FIP2/FIP5 (CLASS I, IN HOST VESICLE SCAVENGING)"],"other_free_text":["Endogenous role: Golgi-to-IMC vesicular transport during daughter cell replication (endodyogeny).","Distinct host-directed role: selective sequestration of host Rab11B-positive recycling vesicles into the parasitophorous vacuole via Rab11-FIP binding.","IMC biogenesis via Rab11B is mechanistically uncoupled from sub-pellicular microtubule formation."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"20686666","id":"PMC_20686666","title":"Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20686666","citation_count":67,"is_preprint":false},{"pmid":"31348812","id":"PMC_31348812","title":"Toxoplasma F-box protein 1 is required for daughter cell scaffold function during parasite replication.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/31348812","citation_count":36,"is_preprint":false},{"pmid":"35274991","id":"PMC_35274991","title":"The Rab11-family interacting proteins reveal selective interaction of mammalian recycling endosomes with the Toxoplasma parasitophorous vacuole in a Rab11- and Arf6-dependent manner.","date":"2022","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/35274991","citation_count":8,"is_preprint":false},{"pmid":"38762629","id":"PMC_38762629","title":"TBC9, an essential TBC-domain protein, regulates early vesicular transport and IMC formation in Toxoplasma gondii.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/38762629","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4390,"output_tokens":1381,"usd":0.016942,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6376,"output_tokens":2617,"usd":0.048653,"stage2_stop_reason":"end_turn"},"total_usd":0.065595,"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\": 2010,\n      \"finding\": \"TgRab11B is an alveolate-specific small GTPase that localizes to the growing end of the inner membrane complex (IMC) during replication of Toxoplasma gondii. Conditional interference with Rab11B function causes a profound defect in IMC biogenesis, demonstrating that Rab11B is required for transport of Golgi-derived vesicles to the nascent IMC of daughter cells. Notably, blocking IMC biogenesis via Rab11B did not affect formation of sub-pellicular microtubules, indicating these two processes are not mechanistically linked.\",\n      \"method\": \"Conditional dominant-negative/interference with Rab11B function; fluorescence localization; genetic epistasis with sub-pellicular microtubule formation\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional loss-of-function with defined cellular phenotype (IMC biogenesis defect) and direct localization, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"20686666\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Localization of the F-box protein TgFBXO1 to the daughter cell scaffold during Toxoplasma replication is dependent on TgRab11B, placing TgRab11B upstream of TgFBXO1 in the vesicular trafficking pathway required for daughter cell scaffold and IMC formation.\",\n      \"method\": \"Genetic epistasis; conditional interference with TgRab11B; fluorescence localization of TgFBXO1 in Rab11B-depleted parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — epistasis/localization experiment in single lab showing Rab11B dependency of TgFBXO1 scaffold localization, single method for this specific finding\",\n      \"pmids\": [\"31348812\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Host cell Rab11B-positive recycling endosomal vesicles are selectively sequestered into the Toxoplasma parasitophorous vacuole (PV). The intra-PV delivery of vesicles bearing class I Rab11-FIPs (FIP1C, FIP2, FIP5) is dependent on Rab11 (including Rab11B) binding, whereas class II FIPs also use Arf6. Cell depletion of Rab11A (a close paralog) selectively reduces intra-PV FIP5 but not FIP3 vesicles, indicating specificity in the host Rab11 vesicle scavenging process.\",\n      \"method\": \"Quantitative fluorescence microscopy; host cell Rab11A/B depletion; FIP mutants abolishing Rab11/Arf6 binding; co-localization analysis of intra-PV vesicles\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal approaches (depletion, binding-mutants, quantitative microscopy) in single lab; finding concerns host Rab11B interaction with Toxoplasma PV\",\n      \"pmids\": [\"35274991\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TBC9, an essential TBC-domain Rab GTPase Activating Protein in Toxoplasma gondii, physically interacts with Rab11B (as well as Rab11A and Rab2) by pull-down assay, linking TBC9 to the Rab11B-dependent pathway for daughter IMC formation and early vesicular transport.\",\n      \"method\": \"Pull-down assay; conditional knockdown of TBC9 with phenotypic analysis of IMC formation and vesicular transport\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pull-down interaction plus functional epistasis context; single lab; direct interaction with Rab11B established by pull-down but full mechanistic detail on Rab11B itself is indirect\",\n      \"pmids\": [\"38762629\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgRab11B is an alveolate-specific small GTPase that mediates vesicular transport from the Golgi to the nascent inner membrane complex (IMC) of daughter cells during Toxoplasma replication; it acts upstream of scaffold effectors such as TgFBXO1, is regulated by the TBC-domain GAP TBC9, and independently of this endogenous role, host Rab11B-positive recycling vesicles are selectively scavenged into the Toxoplasma parasitophorous vacuole via a Rab11-FIP-dependent mechanism.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgRab11B is an alveolate-specific small GTPase that mediates vesicular transport from the Golgi to the nascent inner membrane complex (IMC) of daughter cells during Toxoplasma gondii replication; conditional interference with its function causes a profound IMC biogenesis defect without affecting sub-pellicular microtubule formation, establishing these as mechanistically separable processes [#0]. TgRab11B acts upstream of the F-box scaffold protein TgFBXO1, whose recruitment to the daughter cell scaffold depends on TgRab11B function [#1], and it is a substrate of the essential TBC-domain Rab GAP TBC9, which physically binds TgRab11B and links it to early vesicular transport and daughter IMC formation [#3]. Independently of this endogenous replicative role, host-cell Rab11B-positive recycling endosomal vesicles are selectively scavenged into the Toxoplasma parasitophorous vacuole through a Rab11-FIP-dependent mechanism, with class I FIP delivery requiring Rab11 binding [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established that TgRab11B is required for building the daughter cell inner membrane complex, answering how Golgi-derived vesicles reach the nascent pellicle during endodyogeny and showing that IMC membrane biogenesis is uncoupled from cytoskeletal microtubule formation.\",\n      \"evidence\": \"Conditional dominant-negative interference with fluorescence localization and genetic epistasis against sub-pellicular microtubule formation in T. gondii\",\n      \"pmids\": [\"20686666\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct effectors and vesicle cargo transported by Rab11B not identified\",\n        \"GEF/GAP regulators of the GTPase cycle not defined at this stage\",\n        \"Molecular basis for targeting to the growing IMC end unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed TgRab11B upstream of the scaffold F-box protein TgFBXO1, connecting the GTPase-driven trafficking step to a defined downstream effector required for daughter scaffold and IMC assembly.\",\n      \"evidence\": \"Genetic epistasis with conditional TgRab11B interference and fluorescence localization of TgFBXO1 in Rab11B-depleted parasites\",\n      \"pmids\": [\"31348812\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether TgFBXO1 is a direct Rab11B effector or acts through intermediaries is unresolved\",\n        \"Single method for this specific epistasis finding\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed a distinct host-directed role by showing host Rab11B recycling vesicles are selectively sequestered into the parasitophorous vacuole via a Rab11-FIP-dependent mechanism, defining specificity in parasite scavenging of host endosomal traffic.\",\n      \"evidence\": \"Quantitative fluorescence microscopy with host Rab11A/B depletion, FIP binding mutants, and co-localization of intra-PV vesicles\",\n      \"pmids\": [\"35274991\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Parasite factor(s) that recruit host Rab11B/FIP vesicles to the PV not identified\",\n        \"Functional consequence of host vesicle scavenging for the parasite not established\",\n        \"This role is distinct from the endogenous TgRab11B function and their relationship is not integrated\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified the essential TBC-domain GAP TBC9 as a physical interactor of TgRab11B, providing a candidate regulator of the GTPase cycle governing daughter IMC formation and early vesicular transport.\",\n      \"evidence\": \"Pull-down assay and conditional TBC9 knockdown with phenotypic analysis of IMC formation and vesicular transport in T. gondii\",\n      \"pmids\": [\"38762629\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"TBC9 GAP activity toward Rab11B not demonstrated biochemically\",\n        \"TBC9 also binds Rab11A and Rab2, so Rab11B-specific regulation is not isolated\",\n        \"No structural detail of the interaction\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The GEF that activates TgRab11B, the direct effector repertoire beyond TgFBXO1, and the parasite factors mediating host Rab11B vesicle scavenging remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No GEF identified for the GTPase activation cycle\",\n        \"Direct vesicle cargo and tether proteins unknown\",\n        \"Mechanistic link between endogenous and host-scavenging roles unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 3], \"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:0070938\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005802\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0055085\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"TgFBXO1 (downstream scaffold effector, Rab11B-dependent localization)\",\n      \"TBC9 (TBC-domain Rab GAP, physical interactor)\",\n      \"Rab11-FIPs FIP1C/FIP2/FIP5 (class I, in host vesicle scavenging)\"\n    ],\n    \"other_free_text\": [\n      \"Endogenous role: Golgi-to-IMC vesicular transport during daughter cell replication (endodyogeny).\",\n      \"Distinct host-directed role: selective sequestration of host Rab11B-positive recycling vesicles into the parasitophorous vacuole via Rab11-FIP binding.\",\n      \"IMC biogenesis via Rab11B is mechanistically uncoupled from sub-pellicular microtubule formation.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_320480","name":"RAB11B","product":"ras-related protein RAB11B","uniprot_acc":"A0A125YTY7","chromosome":"TGME49_chrIV","start_pos":313079},{"strain":"GT1","gene_id":"TGGT1_320480","name":null,"product":"Rab11b","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":260360},{"strain":"RH88","gene_id":"TGRH88_006730","name":null,"product":"Rab11b","uniprot_acc":null,"chromosome":"CM023085","start_pos":322408},{"strain":"VEG","gene_id":"TGVEG_320480","name":null,"product":"Rab11b","uniprot_acc":"A0A0F7UVJ8","chromosome":"TGVEG_chrIV","start_pos":304364}]}