{"gene":"TG_239300","gene_symbol":"ICMAP1","run_date":"2026-09-08T12:58:24","timeline":{"discoveries":[{"year":2009,"finding":"TgICMAP1 directly binds to microtubules in vitro, as demonstrated by in vitro microtubule binding assays. When ectopically expressed in mammalian cells, TgICMAP1 stabilizes microtubules. In T. gondii, TgICMAP1 preferentially localizes to the intra-conoid microtubules rather than other tubulin-containing structures in the cell.","method":"In vitro microtubule binding assay; ectopic expression in mammalian cells; localization by fluorescence microscopy in T. gondii","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro microtubule binding assay combined with ectopic expression functional validation and subcellular localization, multiple orthogonal methods in a single focused study","pmids":["19823689"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"ICMAP2 and ICMAP3 (two intraconoidal microtubule-associated proteins related to ICMAP1) are functionally required for sustained rhoptry docking and discharge. Depletion of ICMAP2 causes dissociation of the intraconoidal microtubules (ICMTs), detachment of ICMTs from the conoid, and dispersal of microtubule-associated vesicles (MVs) and rhoptries. ICMAP3 exists in two isoforms: one controlling ICMT length and the other controlling docking of two rhoptries at the apical vesicle. This establishes that ICMTs scaffold iterative rhoptry discharge, which is required for invasion and virulence.","method":"Conditional protein depletion (knockdown), fluorescence microscopy, ultrastructural analysis (electron microscopy), mouse virulence model","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional depletion with specific structural and functional phenotypic readouts (ICMT dissociation, rhoptry docking loss, invasion defect, virulence), multiple orthogonal methods in a single rigorous study","pmids":["38191574"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgICMAP1 is a microtubule-binding protein that directly associates with and stabilizes microtubules and specifically localizes to the intra-conoid microtubules (ICMTs) in T. gondii; the broader family of ICMT-associated proteins (including ICMAP2 and ICMAP3) scaffolds the ICMTs to support iterative rhoptry docking and discharge, which is essential for parasite invasion and virulence."},"narrative":{"mechanistic_narrative":"TgICMAP1 is a microtubule-binding protein of Toxoplasma gondii that directly associates with and stabilizes microtubules and localizes specifically to the intra-conoid microtubules (ICMTs) rather than other tubulin-containing structures of the parasite [PMID:19823689]. It defines a family of ICMT-associated proteins: the related ICMAP2 and ICMAP3 scaffold the ICMTs to support iterative rhoptry docking and discharge, a process essential for host-cell invasion and virulence [PMID:38191574]. Depletion of ICMAP2 dissociates the ICMTs, detaches them from the conoid, and disperses microtubule-associated vesicles and rhoptries, while the two ICMAP3 isoforms respectively control ICMT length and docking of rhoptries at the apical vesicle [PMID:38191574]. Beyond microtubule binding and stabilization by ICMAP1 [PMID:19823689] and the scaffolding role of its relatives [PMID:38191574], no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"It was unknown whether ICMAP1 was a bona fide microtubule-associated protein and which of the parasite's tubulin structures it served; direct binding assays and localization established it as a microtubule-stabilizing protein specific to the intra-conoid microtubules.","evidence":"In vitro microtubule binding assay, ectopic expression in mammalian cells, and fluorescence localization in T. gondii","pmids":["19823689"],"confidence":"High","gaps":["No loss-of-function phenotype for ICMAP1 itself established","The functional consequence of ICMT stabilization for parasite biology not addressed","No structural basis of the microtubule interaction defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"It was unknown what cellular function the intra-conoid microtubules serve; depletion of the related ICMAP2 and ICMAP3 showed the ICMTs scaffold iterative rhoptry docking and discharge required for invasion and virulence.","evidence":"Conditional protein depletion, fluorescence and electron microscopy, and a mouse virulence model","pmids":["38191574"],"confidence":"High","gaps":["ICMAP1's own contribution to rhoptry docking/discharge not directly tested","Molecular mechanism linking ICMT integrity to rhoptry docking not resolved","How the ICMAP proteins are organized on the ICMTs relative to one another not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct functional role of ICMAP1 (as opposed to its relatives ICMAP2/ICMAP3) in ICMT scaffolding and rhoptry discharge remains to be established.","evidence":"","pmids":[],"confidence":"High","gaps":["No conditional loss-of-function or virulence data for ICMAP1 itself","Interplay between ICMAP1 and ICMAP2/ICMAP3 on the ICMTs uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ICMAP2 (RELATED INTRA-CONOID MICROTUBULE-ASSOCIATED PROTEIN) [#1]","ICMAP3 (RELATED INTRA-CONOID MICROTUBULE-ASSOCIATED PROTEIN, TWO ISOFORMS) [#1]"],"other_free_text":["TgICMAP1 stabilizes microtubules when ectopically expressed in mammalian cells [#0]","The ICMAP family scaffolds intra-conoid microtubules to support iterative rhoptry docking and discharge required for invasion and virulence [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"19823689","id":"PMC_19823689","title":"TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19823689","citation_count":25,"is_preprint":false},{"pmid":"38191574","id":"PMC_38191574","title":"Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38191574","citation_count":16,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3279,"output_tokens":779,"usd":0.010761,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5522,"output_tokens":1791,"usd":0.036193,"stage2_stop_reason":"end_turn"},"total_usd":0.046954,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"TgICMAP1 directly binds to microtubules in vitro, as demonstrated by in vitro microtubule binding assays. When ectopically expressed in mammalian cells, TgICMAP1 stabilizes microtubules. In T. gondii, TgICMAP1 preferentially localizes to the intra-conoid microtubules rather than other tubulin-containing structures in the cell.\",\n      \"method\": \"In vitro microtubule binding assay; ectopic expression in mammalian cells; localization by fluorescence microscopy in T. gondii\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro microtubule binding assay combined with ectopic expression functional validation and subcellular localization, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"19823689\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ICMAP2 and ICMAP3 (two intraconoidal microtubule-associated proteins related to ICMAP1) are functionally required for sustained rhoptry docking and discharge. Depletion of ICMAP2 causes dissociation of the intraconoidal microtubules (ICMTs), detachment of ICMTs from the conoid, and dispersal of microtubule-associated vesicles (MVs) and rhoptries. ICMAP3 exists in two isoforms: one controlling ICMT length and the other controlling docking of two rhoptries at the apical vesicle. This establishes that ICMTs scaffold iterative rhoptry discharge, which is required for invasion and virulence.\",\n      \"method\": \"Conditional protein depletion (knockdown), fluorescence microscopy, ultrastructural analysis (electron microscopy), mouse virulence model\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional depletion with specific structural and functional phenotypic readouts (ICMT dissociation, rhoptry docking loss, invasion defect, virulence), multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"38191574\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgICMAP1 is a microtubule-binding protein that directly associates with and stabilizes microtubules and specifically localizes to the intra-conoid microtubules (ICMTs) in T. gondii; the broader family of ICMT-associated proteins (including ICMAP2 and ICMAP3) scaffolds the ICMTs to support iterative rhoptry docking and discharge, which is essential for parasite invasion and virulence.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgICMAP1 is a microtubule-binding protein of Toxoplasma gondii that directly associates with and stabilizes microtubules and localizes specifically to the intra-conoid microtubules (ICMTs) rather than other tubulin-containing structures of the parasite [#0]. It defines a family of ICMT-associated proteins: the related ICMAP2 and ICMAP3 scaffold the ICMTs to support iterative rhoptry docking and discharge, a process essential for host-cell invasion and virulence [#1]. Depletion of ICMAP2 dissociates the ICMTs, detaches them from the conoid, and disperses microtubule-associated vesicles and rhoptries, while the two ICMAP3 isoforms respectively control ICMT length and docking of rhoptries at the apical vesicle [#1]. Beyond microtubule binding and stabilization by ICMAP1 [#0] and the scaffolding role of its relatives [#1], no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"It was unknown whether ICMAP1 was a bona fide microtubule-associated protein and which of the parasite's tubulin structures it served; direct binding assays and localization established it as a microtubule-stabilizing protein specific to the intra-conoid microtubules.\",\n      \"evidence\": \"In vitro microtubule binding assay, ectopic expression in mammalian cells, and fluorescence localization in T. gondii\",\n      \"pmids\": [\"19823689\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No loss-of-function phenotype for ICMAP1 itself established\",\n        \"The functional consequence of ICMT stabilization for parasite biology not addressed\",\n        \"No structural basis of the microtubule interaction defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown what cellular function the intra-conoid microtubules serve; depletion of the related ICMAP2 and ICMAP3 showed the ICMTs scaffold iterative rhoptry docking and discharge required for invasion and virulence.\",\n      \"evidence\": \"Conditional protein depletion, fluorescence and electron microscopy, and a mouse virulence model\",\n      \"pmids\": [\"38191574\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"ICMAP1's own contribution to rhoptry docking/discharge not directly tested\",\n        \"Molecular mechanism linking ICMT integrity to rhoptry docking not resolved\",\n        \"How the ICMAP proteins are organized on the ICMTs relative to one another not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct functional role of ICMAP1 (as opposed to its relatives ICMAP2/ICMAP3) in ICMT scaffolding and rhoptry discharge remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No conditional loss-of-function or virulence data for ICMAP1 itself\",\n        \"Interplay between ICMAP1 and ICMAP2/ICMAP3 on the ICMTs uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0031110\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0020015\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"ICMAP2 (related intra-conoid microtubule-associated protein) [#1]\",\n      \"ICMAP3 (related intra-conoid microtubule-associated protein, two isoforms) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"TgICMAP1 stabilizes microtubules when ectopically expressed in mammalian cells [#0]\",\n      \"The ICMAP family scaffolds intra-conoid microtubules to support iterative rhoptry docking and discharge required for invasion and virulence [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_239300","name":"ICMAP1","product":"intraconoidal microtubule-associated protein ICMAP1","uniprot_acc":"S8GG84","chromosome":"TGME49_chrVI","start_pos":529222},{"strain":"GT1","gene_id":"TGGT1_239300","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":525971},{"strain":"RH88","gene_id":"TGRH88_031650","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023087","start_pos":3163793},{"strain":"VEG","gene_id":"TGVEG_239300A","name":null,"product":"hypothetical protein","uniprot_acc":"V4YSX5","chromosome":"TGVEG_chrVI","start_pos":546608}]}