{"gene":"TG_230220","gene_symbol":"VPS11","run_date":"2026-09-08T11:06:50","timeline":{"discoveries":[{"year":2015,"finding":"TgVps11 is a subunit of the HOPS and CORVET tethering complexes in T. gondii, forming part of the conserved Vps-C core that mediates vesicle transport, tethering, and fusion in the endosomal pathway.","method":"Ortholog identification and functional characterization by conditional knock-down with phenotypic analysis","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knock-down with defined cellular phenotype, single lab, multiple orthogonal phenotypic readouts (motility, invasion, egress, organelle biogenesis)","pmids":["25640905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"finding":"TgVps11 localizes dynamically to Golgi endosomal-related compartments, the parasitophorous vacuole, and immature apical secretory organelles, as determined by direct subcellular localization experiments.","method":"Fluorescence microscopy / subcellular localization","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct imaging of tagged protein, single lab, consistent with functional knock-down data","pmids":["25640905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"finding":"Conditional knock-down of TgVps11 disrupts biogenesis and/or proper subcellular localization of dense granules, rhoptries, and micronemes, establishing an essential role in secretory organelle biogenesis, with downstream loss of parasite motility, invasion, egress, and intracellular growth.","method":"Conditional knock-down (TetO/TetR-DOZI or equivalent inducible system) with phenotypic readouts for organelle biogenesis, motility, invasion, and egress","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional knock-down confirmed with additional HOPS complex subunit mutants, multiple independent phenotypic readouts, single lab but internally replicated across complex members","pmids":["25640905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgVps11 is a core subunit of the HOPS and CORVET vesicle-tethering complexes that localizes to Golgi endosomal compartments, the parasitophorous vacuole, and immature secretory organelles, where it is essential for the biogenesis of all three apical secretory organelle types (dense granules, rhoptries, and micronemes), thereby enabling parasite motility, host cell invasion, egress, and intracellular replication."},"narrative":{"mechanistic_narrative":"TgVps11 is a core subunit of the HOPS and CORVET vesicle-tethering complexes in Toxoplasma gondii, forming part of the conserved Vps-C core that mediates vesicle tethering and fusion within the endosomal pathway [PMID:25640905]. It localizes dynamically to Golgi endosomal-related compartments, the parasitophorous vacuole, and immature apical secretory organelles [PMID:25640905]. Conditional knock-down establishes that TgVps11 is essential for the biogenesis and proper localization of all three apical secretory organelle types — dense granules, rhoptries, and micronemes — with downstream loss of parasite motility, host cell invasion, egress, and intracellular growth [PMID:25640905]. Beyond these findings, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"It was unknown whether the conserved Vps-C tethering machinery operates in apicomplexan parasites; identifying TgVps11 as a HOPS/CORVET subunit established that T. gondii uses this endosomal tethering core.","evidence":"Ortholog identification and functional characterization in T. gondii","pmids":["25640905"],"confidence":"Medium","gaps":["Direct biochemical demonstration of HOPS/CORVET complex assembly and interaction partners not established","Molecular tethering/fusion activity not reconstituted"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"claim":"Where TgVps11 acts within the parasite was unresolved; direct imaging placed it at Golgi endosomal compartments, the parasitophorous vacuole, and immature secretory organelles, linking it spatially to the secretory pathway.","evidence":"Fluorescence microscopy of tagged protein in T. gondii","pmids":["25640905"],"confidence":"Medium","gaps":["Dynamics of compartment transitions not resolved at high temporal resolution","Whether localization reflects HOPS versus CORVET function not distinguished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"claim":"The functional requirement for endosomal tethering in organelle biogenesis was unknown; conditional knock-down showed TgVps11 is essential for biogenesis of dense granules, rhoptries, and micronemes, and consequently for motility, invasion, egress, and replication.","evidence":"Conditional knock-down with phenotypic readouts for organelle biogenesis, motility, invasion, and egress, internally replicated across HOPS complex subunits","pmids":["25640905"],"confidence":"High","gaps":["Molecular cargo/machinery routed through TgVps11-dependent tethering to each organelle not identified","Whether the three organelle biogenesis defects share one common upstream step or diverge is unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical composition, cargo specificity, and mechanism by which TgVps11-containing complexes drive apical organelle biogenesis remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstitution of HOPS/CORVET tethering activity","No identified substrate or cargo","No structural model of the complex"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["HOPS tethering complex","CORVET tethering complex","Vps-C core"],"partners":[],"other_free_text":["Essential for biogenesis/localization of dense granules, rhoptries, and micronemes [#2]","Loss disrupts parasite motility, host cell invasion, egress, and intracellular growth [#2]","Localizes to the parasitophorous vacuole and immature apical secretory organelles [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25640905","id":"PMC_25640905","title":"Toxoplasma gondii Vps11, a subunit of HOPS and CORVET tethering complexes, is essential for the biogenesis of secretory organelles.","date":"2015","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25640905","citation_count":45,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2995,"output_tokens":828,"usd":0.010703,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5617,"output_tokens":1884,"usd":0.037593,"stage2_stop_reason":"end_turn"},"total_usd":0.048296,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"TgVps11 is a subunit of the HOPS and CORVET tethering complexes in T. gondii, forming part of the conserved Vps-C core that mediates vesicle transport, tethering, and fusion in the endosomal pathway.\",\n      \"method\": \"Ortholog identification and functional characterization by conditional knock-down with phenotypic analysis\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knock-down with defined cellular phenotype, single lab, multiple orthogonal phenotypic readouts (motility, invasion, egress, organelle biogenesis)\",\n      \"pmids\": [\"25640905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TgVps11 localizes dynamically to Golgi endosomal-related compartments, the parasitophorous vacuole, and immature apical secretory organelles, as determined by direct subcellular localization experiments.\",\n      \"method\": \"Fluorescence microscopy / subcellular localization\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging of tagged protein, single lab, consistent with functional knock-down data\",\n      \"pmids\": [\"25640905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Conditional knock-down of TgVps11 disrupts biogenesis and/or proper subcellular localization of dense granules, rhoptries, and micronemes, establishing an essential role in secretory organelle biogenesis, with downstream loss of parasite motility, invasion, egress, and intracellular growth.\",\n      \"method\": \"Conditional knock-down (TetO/TetR-DOZI or equivalent inducible system) with phenotypic readouts for organelle biogenesis, motility, invasion, and egress\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional knock-down confirmed with additional HOPS complex subunit mutants, multiple independent phenotypic readouts, single lab but internally replicated across complex members\",\n      \"pmids\": [\"25640905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgVps11 is a core subunit of the HOPS and CORVET vesicle-tethering complexes that localizes to Golgi endosomal compartments, the parasitophorous vacuole, and immature secretory organelles, where it is essential for the biogenesis of all three apical secretory organelle types (dense granules, rhoptries, and micronemes), thereby enabling parasite motility, host cell invasion, egress, and intracellular replication.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgVps11 is a core subunit of the HOPS and CORVET vesicle-tethering complexes in Toxoplasma gondii, forming part of the conserved Vps-C core that mediates vesicle tethering and fusion within the endosomal pathway [#0]. It localizes dynamically to Golgi endosomal-related compartments, the parasitophorous vacuole, and immature apical secretory organelles [#1]. Conditional knock-down establishes that TgVps11 is essential for the biogenesis and proper localization of all three apical secretory organelle types — dense granules, rhoptries, and micronemes — with downstream loss of parasite motility, host cell invasion, egress, and intracellular growth [#2]. Beyond these findings, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unknown whether the conserved Vps-C tethering machinery operates in apicomplexan parasites; identifying TgVps11 as a HOPS/CORVET subunit established that T. gondii uses this endosomal tethering core.\",\n      \"evidence\": \"Ortholog identification and functional characterization in T. gondii\",\n      \"pmids\": [\"25640905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical demonstration of HOPS/CORVET complex assembly and interaction partners not established\",\n        \"Molecular tethering/fusion activity not reconstituted\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Where TgVps11 acts within the parasite was unresolved; direct imaging placed it at Golgi endosomal compartments, the parasitophorous vacuole, and immature secretory organelles, linking it spatially to the secretory pathway.\",\n      \"evidence\": \"Fluorescence microscopy of tagged protein in T. gondii\",\n      \"pmids\": [\"25640905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Dynamics of compartment transitions not resolved at high temporal resolution\",\n        \"Whether localization reflects HOPS versus CORVET function not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"The functional requirement for endosomal tethering in organelle biogenesis was unknown; conditional knock-down showed TgVps11 is essential for biogenesis of dense granules, rhoptries, and micronemes, and consequently for motility, invasion, egress, and replication.\",\n      \"evidence\": \"Conditional knock-down with phenotypic readouts for organelle biogenesis, motility, invasion, and egress, internally replicated across HOPS complex subunits\",\n      \"pmids\": [\"25640905\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular cargo/machinery routed through TgVps11-dependent tethering to each organelle not identified\",\n        \"Whether the three organelle biogenesis defects share one common upstream step or diverge is unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical composition, cargo specificity, and mechanism by which TgVps11-containing complexes drive apical organelle biogenesis remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reconstitution of HOPS/CORVET tethering activity\",\n        \"No identified substrate or cargo\",\n        \"No structural model of the complex\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004871\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"HOPS tethering complex\",\n      \"CORVET tethering complex\",\n      \"Vps-C core\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Essential for biogenesis/localization of dense granules, rhoptries, and micronemes [#2]\",\n      \"Loss disrupts parasite motility, host cell invasion, egress, and intracellular growth [#2]\",\n      \"Localizes to the parasitophorous vacuole and immature apical secretory organelles [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_230220","name":"VPS11","product":"vacuolar protein sorting-associated protein 11","uniprot_acc":"S8F315","chromosome":"TGME49_chrVIII","start_pos":690193},{"strain":"GT1","gene_id":"TGGT1_230220","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":687373},{"strain":"RH88","gene_id":"TGRH88_074720","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":5798798},{"strain":"VEG","gene_id":"TGVEG_230220","name":null,"product":"putative vacuolar protein sorting 11 carboxy-terminal protein","uniprot_acc":"V4ZUI3","chromosome":"TGVEG_chrVIII","start_pos":697020}]}