{"gene":"TG_321620","gene_symbol":"DRPB","run_date":"2026-09-08T15:15:14","timeline":{"discoveries":[{"year":2009,"finding":"DrpB is an alveolate-specific dynamin-related protein that localizes to a cytoplasmic region close to the Golgi; it disperses during replication and reforms after daughter cell assembly, and conditional ablation of DrpB results in mature daughter parasites completely devoid of micronemes and rhoptries, with invasion-related secretory proteins mistargeted to the constitutive secretory pathway.","method":"Conditional loss-of-function (conditional ablation), fluorescence localization, phenotypic analysis of secretory organelle biogenesis","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional genetic ablation with defined organelle-biogenesis phenotype, protein localization, and pathway placement (regulated vs. constitutive secretory pathway), single lab but multiple orthogonal methods","pmids":["19217293"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Expression of a DrpB dominant-negative mutant increases T. gondii ingestion of host-derived proteins, indicating that DrpB is not required for parasite endocytosis (negative finding); endocytic trafficking of ingested host proteins intersects with exocytic microneme protein trafficking through early/late endosome-like compartments (ELCs), and DrpB functions in the exocytic arm (microneme/rhoptry biogenesis) within this shared trafficking route.","method":"Conditional dominant-negative expression, colocalization of host-derived proteins with immature microneme/rhoptry markers, live-cell trafficking assays","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant-negative conditional expression plus colocalization with pathway markers, single lab","pmids":["29437275"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"DrpB is an alveolate-specific dynamin-related mechanoenzyme that localizes near the Golgi and is essential for generating vesicles that give rise to the regulated secretory organelles (micronemes and rhoptries) during daughter-cell assembly, acting at the intersection of endocytic and exocytic trafficking routes through early/late endosome-like compartments, but is not required for endocytosis of host-derived proteins."},"narrative":{"mechanistic_narrative":"DrpB is an alveolate-specific dynamin-related protein that drives biogenesis of the regulated secretory organelles in Toxoplasma gondii [PMID:19217293]. It localizes to a cytoplasmic region close to the Golgi, dispersing during replication and reforming after daughter-cell assembly, consistent with a vesicle-generating mechanoenzyme acting during the secretory-organelle assembly phase of the cell cycle [PMID:19217293]. Conditional ablation of DrpB yields mature daughter parasites completely devoid of micronemes and rhoptries, with invasion-related secretory cargo mistargeted to the constitutive secretory pathway, placing DrpB at the step that segregates regulated from constitutive secretion [PMID:19217293]. DrpB operates specifically in the exocytic arm of a trafficking route shared with host-protein endocytosis through early/late endosome-like compartments; it is dispensable for endocytosis of host-derived proteins [PMID:29437275]. Beyond these findings, the enzymatic and structural details of DrpB have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Establishing whether a dedicated machinery generates the vesicles that build the invasion organelles, this work identified DrpB as an alveolate-specific dynamin-related protein essential for microneme and rhoptry biogenesis.","evidence":"Conditional ablation, fluorescence localization, and secretory-organelle phenotyping in T. gondii","pmids":["19217293"],"confidence":"High","gaps":["No demonstration of the biochemical mechanoenzyme activity (GTP hydrolysis or membrane scission)","Direct binding partners and recruitment mechanism to the Golgi-proximal site unresolved","No structural model of DrpB"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"To determine whether DrpB acts broadly across membrane trafficking or specifically in exocytosis, a dominant-negative mutant showed DrpB is dispensable for host-protein endocytosis and functions in the exocytic arm of a route shared with endocytosis through endosome-like compartments.","evidence":"Conditional dominant-negative expression with colocalization of host-derived proteins and immature organelle markers plus live-cell trafficking in T. gondii","pmids":["29437275"],"confidence":"Medium","gaps":["Dominant-negative approach does not pinpoint the direct molecular step DrpB catalyzes","Molecular components of the shared endosome-like compartment engaged by DrpB not defined","Whether DrpB directly deforms/scissions vesicles at these compartments not shown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct biochemical activity of DrpB, its recruitment machinery, and the identity of its membrane and protein partners remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No demonstrated GTPase or membrane-scission activity in the corpus","No identified interacting proteins or adaptors","No structural characterization"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Essential for biogenesis of micronemes and rhoptries; ablation causes mistargeting of regulated secretory cargo to the constitutive pathway [#0]","Golgi-proximal, cell-cycle-regulated localization: disperses during replication, reforms after daughter-cell assembly [#0]","Functions in the exocytic arm of a trafficking route shared with host-protein endocytosis via early/late endosome-like compartments; not required for endocytosis [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"19217293","id":"PMC_19217293","title":"A dynamin is required for the biogenesis of secretory organelles in Toxoplasma gondii.","date":"2009","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/19217293","citation_count":108,"is_preprint":false},{"pmid":"29437275","id":"PMC_29437275","title":"Intersection of endocytic and exocytic systems in Toxoplasma gondii.","date":"2018","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/29437275","citation_count":49,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3412,"output_tokens":676,"usd":0.010188,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5440,"output_tokens":1749,"usd":0.035463,"stage2_stop_reason":"end_turn"},"total_usd":0.045651,"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\": 2009,\n      \"finding\": \"DrpB is an alveolate-specific dynamin-related protein that localizes to a cytoplasmic region close to the Golgi; it disperses during replication and reforms after daughter cell assembly, and conditional ablation of DrpB results in mature daughter parasites completely devoid of micronemes and rhoptries, with invasion-related secretory proteins mistargeted to the constitutive secretory pathway.\",\n      \"method\": \"Conditional loss-of-function (conditional ablation), fluorescence localization, phenotypic analysis of secretory organelle biogenesis\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional genetic ablation with defined organelle-biogenesis phenotype, protein localization, and pathway placement (regulated vs. constitutive secretory pathway), single lab but multiple orthogonal methods\",\n      \"pmids\": [\"19217293\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Expression of a DrpB dominant-negative mutant increases T. gondii ingestion of host-derived proteins, indicating that DrpB is not required for parasite endocytosis (negative finding); endocytic trafficking of ingested host proteins intersects with exocytic microneme protein trafficking through early/late endosome-like compartments (ELCs), and DrpB functions in the exocytic arm (microneme/rhoptry biogenesis) within this shared trafficking route.\",\n      \"method\": \"Conditional dominant-negative expression, colocalization of host-derived proteins with immature microneme/rhoptry markers, live-cell trafficking assays\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant-negative conditional expression plus colocalization with pathway markers, single lab\",\n      \"pmids\": [\"29437275\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"DrpB is an alveolate-specific dynamin-related mechanoenzyme that localizes near the Golgi and is essential for generating vesicles that give rise to the regulated secretory organelles (micronemes and rhoptries) during daughter-cell assembly, acting at the intersection of endocytic and exocytic trafficking routes through early/late endosome-like compartments, but is not required for endocytosis of host-derived proteins.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DrpB is an alveolate-specific dynamin-related protein that drives biogenesis of the regulated secretory organelles in Toxoplasma gondii [#0]. It localizes to a cytoplasmic region close to the Golgi, dispersing during replication and reforming after daughter-cell assembly, consistent with a vesicle-generating mechanoenzyme acting during the secretory-organelle assembly phase of the cell cycle [#0]. Conditional ablation of DrpB yields mature daughter parasites completely devoid of micronemes and rhoptries, with invasion-related secretory cargo mistargeted to the constitutive secretory pathway, placing DrpB at the step that segregates regulated from constitutive secretion [#0]. DrpB operates specifically in the exocytic arm of a trafficking route shared with host-protein endocytosis through early/late endosome-like compartments; it is dispensable for endocytosis of host-derived proteins [#1]. Beyond these findings, the enzymatic and structural details of DrpB have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing whether a dedicated machinery generates the vesicles that build the invasion organelles, this work identified DrpB as an alveolate-specific dynamin-related protein essential for microneme and rhoptry biogenesis.\",\n      \"evidence\": \"Conditional ablation, fluorescence localization, and secretory-organelle phenotyping in T. gondii\",\n      \"pmids\": [\"19217293\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No demonstration of the biochemical mechanoenzyme activity (GTP hydrolysis or membrane scission)\",\n        \"Direct binding partners and recruitment mechanism to the Golgi-proximal site unresolved\",\n        \"No structural model of DrpB\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To determine whether DrpB acts broadly across membrane trafficking or specifically in exocytosis, a dominant-negative mutant showed DrpB is dispensable for host-protein endocytosis and functions in the exocytic arm of a route shared with endocytosis through endosome-like compartments.\",\n      \"evidence\": \"Conditional dominant-negative expression with colocalization of host-derived proteins and immature organelle markers plus live-cell trafficking in T. gondii\",\n      \"pmids\": [\"29437275\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Dominant-negative approach does not pinpoint the direct molecular step DrpB catalyzes\",\n        \"Molecular components of the shared endosome-like compartment engaged by DrpB not defined\",\n        \"Whether DrpB directly deforms/scissions vesicles at these compartments not shown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical activity of DrpB, its recruitment machinery, and the identity of its membrane and protein partners remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No demonstrated GTPase or membrane-scission activity in the corpus\",\n        \"No identified interacting proteins or adaptors\",\n        \"No structural characterization\"\n      ],\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    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0045053\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Essential for biogenesis of micronemes and rhoptries; ablation causes mistargeting of regulated secretory cargo to the constitutive pathway [#0]\",\n      \"Golgi-proximal, cell-cycle-regulated localization: disperses during replication, reforms after daughter-cell assembly [#0]\",\n      \"Functions in the exocytic arm of a trafficking route shared with host-protein endocytosis via early/late endosome-like compartments; not required for endocytosis [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_321620","name":"DRPB","product":"dynamin-related protein DRPB","uniprot_acc":"A0A125YT62","chromosome":"TGME49_chrIb","start_pos":1689535},{"strain":"GT1","gene_id":"TGGT1_321620","name":null,"product":"dynamin-related protein DRPB","uniprot_acc":null,"chromosome":"TGGT1_chrIb","start_pos":1696372},{"strain":"RH88","gene_id":"TGRH88_021020","name":null,"product":"dynamin-related protein DRPB","uniprot_acc":null,"chromosome":"CM023082","start_pos":268704},{"strain":"VEG","gene_id":"TGVEG_321620","name":null,"product":"dynamin-related protein DRPB","uniprot_acc":"B9Q341","chromosome":"TGVEG_chrIb","start_pos":1707616}]}