{"gene":"TG_261080","gene_symbol":"CRMPA","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2022,"finding":"TgCRMPs are membrane-bound proteins forming part of a large complex (the CRMP complex) that is essential for rhoptry secretion and invasion in Toxoplasma gondii. Unlike previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery but only transiently associate with the exocytic site prior to invasion. CRMPa shares similarities with GPCR proteins, and CRMPs and their partners contain putative host cell-binding domains, implying the complex acts as a host-molecular sensor to trigger rhoptry exocytosis upon host cell contact.","method":"Tetrahymena-based transcriptomic screen, expansion microscopy, cryo-electron tomography, functional loss-of-function analysis in Toxoplasma gondii","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (transcriptomic screen, expansion microscopy, cryo-ET, functional KO with invasion phenotype) in a single rigorous study","pmids":["36245278"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"CRMPA (TGGT1_261080) and CRMPB (TGGT1_292020) form a protein complex together with MIC15 and a thrombospondin type 1 domain-containing protein (TSP1). Disruption of this complex results in a block of rhoptry secretion and complete failure of host cell invasion.","method":"Co-immunoprecipitation/complex identification, conditional disruption of complex components with rhoptry secretion and invasion assays as phenotypic readouts","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification, loss-of-function with defined molecular phenotype (rhoptry secretion block) and cellular phenotype (invasion failure), replicated across two independent studies","pmids":["36602948"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"current_model":"CRMPA is a membrane-bound, GPCR-like apicomplexan protein that forms a conserved apical complex with CRMPB, MIC15, and TSP1; this complex transiently associates with the rhoptry exocytic site prior to invasion and acts as a host-molecular sensor to trigger regulated rhoptry exocytosis upon host cell contact, without being required for the structural assembly of the secretion machinery itself."},"narrative":{"mechanistic_narrative":"CRMPA is a membrane-bound, GPCR-like apicomplexan protein that functions as an essential trigger for regulated rhoptry secretion during host cell invasion by Toxoplasma gondii [PMID:36245278]. It assembles into a conserved apical complex (the CRMP complex) together with CRMPB, MIC15, and a thrombospondin type 1 domain-containing protein (TSP1); disruption of any of these components blocks rhoptry secretion and causes complete failure of host cell invasion [PMID:36602948]. Rather than building the rhoptry secretion machinery itself, CRMPA and its partners only transiently associate with the exocytic site prior to invasion, and the presence of putative host cell-binding domains together with CRMPA's GPCR-like features indicates the complex acts as a host-molecular sensor that couples host cell contact to triggered rhoptry exocytosis [PMID:36245278]. Beyond this sensing-and-triggering role, no direct ligand, downstream signaling partner, or structural model has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Established that TgCRMPs form a membrane-bound complex essential for rhoptry secretion, and distinguished them from structural machinery factors by showing they only transiently associate with the exocytic site — reframing them as a host-sensing trigger rather than part of the secretion apparatus.","evidence":"Tetrahymena-based transcriptomic screen, expansion microscopy, cryo-electron tomography, and loss-of-function analysis in Toxoplasma gondii","pmids":["36245278"],"confidence":"High","gaps":["No host ligand or receptor for the putative host-binding domains identified","The signal-transduction mechanism linking CRMPA's GPCR-like features to exocytosis triggering is undefined","No structural model of the complex or its association with the exocytic site"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Defined the molecular composition of the CRMP complex — CRMPA, CRMPB, MIC15, and TSP1 — and demonstrated that disrupting the complex abolishes both rhoptry secretion and invasion, confirming its essential and non-redundant role.","evidence":"Co-immunoprecipitation/complex identification with conditional disruption of components and rhoptry secretion and invasion assays in T. gondii RH","pmids":["36602948"],"confidence":"High","gaps":["Stoichiometry and spatial architecture of the four-subunit complex not resolved","Individual contributions of CRMPA versus its partners to host sensing not dissected","Whether the same complex composition holds across other strains or species not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":null,"claim":"The host molecular cue detected by the complex and the downstream signaling events that convert host contact into rhoptry exocytosis remain unidentified.","evidence":"","pmids":[],"confidence":"High","gaps":["No host ligand identified for the putative host cell-binding domains","No signaling intermediates linking CRMPA to the exocytic machinery characterized","No structural basis for complex assembly or exocytic-site recruitment"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CRMP complex (CRMPA, CRMPB, MIC15, TSP1)"],"partners":["CRMPB","MIC15","TSP1 (THROMBOSPONDIN TYPE 1 DOMAIN-CONTAINING PROTEIN)"],"other_free_text":["CRMPA (TGGT1_261080) shares similarities with GPCR proteins and, together with its partners, contains putative host cell-binding domains, consistent with a host-molecular sensor function [#0].","The CRMP complex transiently associates with the rhoptry exocytic site prior to invasion but is not required for assembly of the secretion machinery itself [#0].","Conditional disruption of complex components blocks rhoptry secretion and causes complete failure of host cell invasion [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"36245278","id":"PMC_36245278","title":"An apical membrane complex for triggering rhoptry exocytosis and invasion in Toxoplasma.","date":"2022","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/36245278","citation_count":30,"is_preprint":false},{"pmid":"36602948","id":"PMC_36602948","title":"A central CRMP complex essential for invasion in Toxoplasma gondii.","date":"2023","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/36602948","citation_count":23,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3284,"output_tokens":734,"usd":0.010431,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5490,"output_tokens":1804,"usd":0.036275,"stage2_stop_reason":"end_turn"},"total_usd":0.046706,"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\": 2022,\n      \"finding\": \"TgCRMPs are membrane-bound proteins forming part of a large complex (the CRMP complex) that is essential for rhoptry secretion and invasion in Toxoplasma gondii. Unlike previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery but only transiently associate with the exocytic site prior to invasion. CRMPa shares similarities with GPCR proteins, and CRMPs and their partners contain putative host cell-binding domains, implying the complex acts as a host-molecular sensor to trigger rhoptry exocytosis upon host cell contact.\",\n      \"method\": \"Tetrahymena-based transcriptomic screen, expansion microscopy, cryo-electron tomography, functional loss-of-function analysis in Toxoplasma gondii\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (transcriptomic screen, expansion microscopy, cryo-ET, functional KO with invasion phenotype) in a single rigorous study\",\n      \"pmids\": [\"36245278\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CRMPA (TGGT1_261080) and CRMPB (TGGT1_292020) form a protein complex together with MIC15 and a thrombospondin type 1 domain-containing protein (TSP1). Disruption of this complex results in a block of rhoptry secretion and complete failure of host cell invasion.\",\n      \"method\": \"Co-immunoprecipitation/complex identification, conditional disruption of complex components with rhoptry secretion and invasion assays as phenotypic readouts\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification, loss-of-function with defined molecular phenotype (rhoptry secretion block) and cellular phenotype (invasion failure), replicated across two independent studies\",\n      \"pmids\": [\"36602948\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CRMPA is a membrane-bound, GPCR-like apicomplexan protein that forms a conserved apical complex with CRMPB, MIC15, and TSP1; this complex transiently associates with the rhoptry exocytic site prior to invasion and acts as a host-molecular sensor to trigger regulated rhoptry exocytosis upon host cell contact, without being required for the structural assembly of the secretion machinery itself.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CRMPA is a membrane-bound, GPCR-like apicomplexan protein that functions as an essential trigger for regulated rhoptry secretion during host cell invasion by Toxoplasma gondii [#0]. It assembles into a conserved apical complex (the CRMP complex) together with CRMPB, MIC15, and a thrombospondin type 1 domain-containing protein (TSP1); disruption of any of these components blocks rhoptry secretion and causes complete failure of host cell invasion [#1]. Rather than building the rhoptry secretion machinery itself, CRMPA and its partners only transiently associate with the exocytic site prior to invasion, and the presence of putative host cell-binding domains together with CRMPA's GPCR-like features indicates the complex acts as a host-molecular sensor that couples host cell contact to triggered rhoptry exocytosis [#0]. Beyond this sensing-and-triggering role, no direct ligand, downstream signaling partner, or structural model has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Established that TgCRMPs form a membrane-bound complex essential for rhoptry secretion, and distinguished them from structural machinery factors by showing they only transiently associate with the exocytic site — reframing them as a host-sensing trigger rather than part of the secretion apparatus.\",\n      \"evidence\": \"Tetrahymena-based transcriptomic screen, expansion microscopy, cryo-electron tomography, and loss-of-function analysis in Toxoplasma gondii\",\n      \"pmids\": [\"36245278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No host ligand or receptor for the putative host-binding domains identified\",\n        \"The signal-transduction mechanism linking CRMPA's GPCR-like features to exocytosis triggering is undefined\",\n        \"No structural model of the complex or its association with the exocytic site\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the molecular composition of the CRMP complex — CRMPA, CRMPB, MIC15, and TSP1 — and demonstrated that disrupting the complex abolishes both rhoptry secretion and invasion, confirming its essential and non-redundant role.\",\n      \"evidence\": \"Co-immunoprecipitation/complex identification with conditional disruption of components and rhoptry secretion and invasion assays in T. gondii RH\",\n      \"pmids\": [\"36602948\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and spatial architecture of the four-subunit complex not resolved\",\n        \"Individual contributions of CRMPA versus its partners to host sensing not dissected\",\n        \"Whether the same complex composition holds across other strains or species not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The host molecular cue detected by the complex and the downstream signaling events that convert host contact into rhoptry exocytosis remain unidentified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No host ligand identified for the putative host cell-binding domains\",\n        \"No signaling intermediates linking CRMPA to the exocytic machinery characterized\",\n        \"No structural basis for complex assembly or exocytic-site recruitment\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004930\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035891\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"complexes\": [\n      \"CRMP complex (CRMPA, CRMPB, MIC15, TSP1)\"\n    ],\n    \"partners\": [\n      \"CRMPB\",\n      \"MIC15\",\n      \"TSP1 (thrombospondin type 1 domain-containing protein)\"\n    ],\n    \"other_free_text\": [\n      \"CRMPA (TGGT1_261080) shares similarities with GPCR proteins and, together with its partners, contains putative host cell-binding domains, consistent with a host-molecular sensor function [#0].\",\n      \"The CRMP complex transiently associates with the rhoptry exocytic site prior to invasion but is not required for assembly of the secretion machinery itself [#0].\",\n      \"Conditional disruption of complex components blocks rhoptry secretion and causes complete failure of host cell invasion [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_261080","name":"CRMPA","product":"cysteine repeat modular protein CRMPA","uniprot_acc":"S8F7M3","chromosome":"TGME49_chrVIIb","start_pos":1849025},{"strain":"GT1","gene_id":"TGGT1_261080","name":"CRMPA","product":"cysteine repeat modular protein CRMPA","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":1823412},{"strain":"RH88","gene_id":"TGRH88_069420","name":null,"product":"kringle domain-containing protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":1868735},{"strain":"VEG","gene_id":"TGVEG_261080","name":null,"product":"kringle domain-containing protein","uniprot_acc":"V4ZA01","chromosome":"TGVEG_chrVIIb","start_pos":1865400}]}