{"gene":"TG_292020","gene_symbol":"CRMPB","run_date":"2026-09-08T14:08:30","timeline":{"discoveries":[{"year":2022,"finding":"TgCRMPs (including CRMPB) are membrane-bound proteins that form a large complex (CRMP complex) essential for rhoptry secretion and host cell invasion in Toxoplasma gondii. Unlike previously described rhoptry exocytic factors, TgCRMPs are not required for assembly of the rhoptry secretion machinery but transiently associate with the exocytic site prior to invasion, consistent with a role as a host-molecular sensor that ensures rhoptry exocytosis occurs upon host cell contact.","method":"Tetrahymena-based transcriptomic screen, conditional knockdown/disruption, expansion microscopy, cryo-electron tomography","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal imaging and functional methods (cryo-ET, expansion microscopy, loss-of-function) in a single rigorous study establishing complex membership, localization, and distinct functional requirement","pmids":["36245278"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"CRMPB (TGGT1_292020) forms a complex with CRMPA (TGGT1_261080), MIC15, and a thrombospondin type 1 domain-containing protein (TSP1). Disruption of this complex blocks rhoptry secretion and renders parasites unable to invade host cells, establishing the CRMP complex as a central, apicomplexan-conserved invasion complex.","method":"Co-immunoprecipitation / pulldown to define complex composition; conditional disruption with rhoptry secretion and invasion assays as functional readouts","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex identification combined with loss-of-function showing specific block in rhoptry secretion and invasion, replicating and extending findings from an independent lab","pmids":["36602948"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"current_model":"CRMPB is a membrane-bound apicomplexan-specific protein that forms a conserved complex with CRMPA, MIC15, and TSP1 at the apical exocytic site in Toxoplasma gondii; this CRMP complex is not required for assembly of the rhoptry secretion machinery itself but transiently associates with the secretion site prior to invasion and is essential for triggering rhoptry exocytosis upon host cell contact, thereby acting as a host-molecular sensor that couples host recognition to rhoptry discharge and invasion."},"narrative":{"mechanistic_narrative":"CRMPB is a membrane-bound, apicomplexan-conserved protein of Toxoplasma gondii that functions within a multiprotein complex controlling rhoptry secretion and host cell invasion [PMID:36245278, PMID:36602948]. Together with CRMPA, MIC15, and a thrombospondin type 1 domain-containing protein (TSP1), CRMPB forms the CRMP complex, whose disruption blocks rhoptry exocytosis and renders parasites unable to invade host cells [PMID:36602948]. Rather than building the rhoptry secretion machinery itself, the CRMP complex transiently associates with the apical exocytic site prior to invasion, consistent with a role as a host-molecular sensor that couples host cell contact to rhoptry discharge [PMID:36245278]. Beyond its membership in this complex and its requirement for triggering rhoptry secretion, no further biochemical or structural detail of CRMPB has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"It was unknown whether an upstream factor distinct from the rhoptry secretion machinery couples host contact to exocytosis; this work established that membrane-bound TgCRMPs form a complex that transiently docks at the exocytic site and is required for rhoptry secretion and invasion without being needed to assemble the secretion apparatus.","evidence":"Tetrahymena-based transcriptomic screen, conditional knockdown/disruption, expansion microscopy, and cryo-electron tomography in Toxoplasma gondii","pmids":["36245278"],"confidence":"High","gaps":["The molecular identity of the host signal or receptor sensed by the complex is undefined","How CRMPB is targeted to and transiently associates with the exocytic site is not resolved","The specific contribution of CRMPB versus other complex members is not dissected"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"The precise composition of the invasion complex was undefined; reciprocal pulldowns established that CRMPB associates with CRMPA, MIC15, and TSP1, and that disrupting this complex specifically blocks rhoptry secretion and invasion, defining it as a conserved apicomplexan invasion complex.","evidence":"Co-immunoprecipitation/pulldown to define complex composition plus conditional disruption with rhoptry secretion and invasion assays in Toxoplasma gondii RH","pmids":["36602948"],"confidence":"High","gaps":["The stoichiometry and structural architecture of the complex are unknown","The molecular mechanism by which complex integrity triggers rhoptry exocytosis is not established","Direct binding interfaces between CRMPB and each partner are not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":null,"claim":"The nature of the host molecular cue detected by the CRMP complex and the signaling steps linking that recognition to rhoptry discharge remain unknown.","evidence":"Not established in the available corpus","pmids":[],"confidence":"High","gaps":["No host ligand or receptor for the putative sensor function has been identified","The signal transduction pathway from host contact to exocytosis is uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CRMP complex (CRMPA, CRMPB, MIC15, TSP1)"],"partners":["CRMPA (TGGT1_261080)","MIC15","TSP1 (THROMBOSPONDIN TYPE 1 DOMAIN-CONTAINING PROTEIN)"],"other_free_text":["Membrane-bound, apicomplexan-conserved protein; TGGT1_292020","Not required for assembly of the rhoptry secretion machinery but transiently associates with the exocytic site prior to invasion, consistent with a host-molecular sensor role [#0]"]},"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":740,"usd":0.010476,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5509,"output_tokens":1671,"usd":0.03466,"stage2_stop_reason":"end_turn"},"total_usd":0.045136,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"TgCRMPs (including CRMPB) are membrane-bound proteins that form a large complex (CRMP complex) essential for rhoptry secretion and host cell invasion in Toxoplasma gondii. Unlike previously described rhoptry exocytic factors, TgCRMPs are not required for assembly of the rhoptry secretion machinery but transiently associate with the exocytic site prior to invasion, consistent with a role as a host-molecular sensor that ensures rhoptry exocytosis occurs upon host cell contact.\",\n      \"method\": \"Tetrahymena-based transcriptomic screen, conditional knockdown/disruption, expansion microscopy, cryo-electron tomography\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal imaging and functional methods (cryo-ET, expansion microscopy, loss-of-function) in a single rigorous study establishing complex membership, localization, and distinct functional requirement\",\n      \"pmids\": [\"36245278\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CRMPB (TGGT1_292020) forms a complex with CRMPA (TGGT1_261080), MIC15, and a thrombospondin type 1 domain-containing protein (TSP1). Disruption of this complex blocks rhoptry secretion and renders parasites unable to invade host cells, establishing the CRMP complex as a central, apicomplexan-conserved invasion complex.\",\n      \"method\": \"Co-immunoprecipitation / pulldown to define complex composition; conditional disruption with rhoptry secretion and invasion assays as functional readouts\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex identification combined with loss-of-function showing specific block in rhoptry secretion and invasion, replicating and extending findings from an independent lab\",\n      \"pmids\": [\"36602948\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CRMPB is a membrane-bound apicomplexan-specific protein that forms a conserved complex with CRMPA, MIC15, and TSP1 at the apical exocytic site in Toxoplasma gondii; this CRMP complex is not required for assembly of the rhoptry secretion machinery itself but transiently associates with the secretion site prior to invasion and is essential for triggering rhoptry exocytosis upon host cell contact, thereby acting as a host-molecular sensor that couples host recognition to rhoptry discharge and invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CRMPB is a membrane-bound, apicomplexan-conserved protein of Toxoplasma gondii that functions within a multiprotein complex controlling rhoptry secretion and host cell invasion [#0, #1]. Together with CRMPA, MIC15, and a thrombospondin type 1 domain-containing protein (TSP1), CRMPB forms the CRMP complex, whose disruption blocks rhoptry exocytosis and renders parasites unable to invade host cells [#1]. Rather than building the rhoptry secretion machinery itself, the CRMP complex transiently associates with the apical exocytic site prior to invasion, consistent with a role as a host-molecular sensor that couples host cell contact to rhoptry discharge [#0]. Beyond its membership in this complex and its requirement for triggering rhoptry secretion, no further biochemical or structural detail of CRMPB has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"It was unknown whether an upstream factor distinct from the rhoptry secretion machinery couples host contact to exocytosis; this work established that membrane-bound TgCRMPs form a complex that transiently docks at the exocytic site and is required for rhoptry secretion and invasion without being needed to assemble the secretion apparatus.\",\n      \"evidence\": \"Tetrahymena-based transcriptomic screen, conditional knockdown/disruption, expansion microscopy, and cryo-electron tomography in Toxoplasma gondii\",\n      \"pmids\": [\"36245278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular identity of the host signal or receptor sensed by the complex is undefined\",\n        \"How CRMPB is targeted to and transiently associates with the exocytic site is not resolved\",\n        \"The specific contribution of CRMPB versus other complex members is not dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The precise composition of the invasion complex was undefined; reciprocal pulldowns established that CRMPB associates with CRMPA, MIC15, and TSP1, and that disrupting this complex specifically blocks rhoptry secretion and invasion, defining it as a conserved apicomplexan invasion complex.\",\n      \"evidence\": \"Co-immunoprecipitation/pulldown to define complex composition plus conditional disruption with rhoptry secretion and invasion assays in Toxoplasma gondii RH\",\n      \"pmids\": [\"36602948\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The stoichiometry and structural architecture of the complex are unknown\",\n        \"The molecular mechanism by which complex integrity triggers rhoptry exocytosis is not established\",\n        \"Direct binding interfaces between CRMPB and each partner are not mapped\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The nature of the host molecular cue detected by the CRMP complex and the signaling steps linking that recognition to rhoptry discharge remain unknown.\",\n      \"evidence\": \"Not established in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No host ligand or receptor for the putative sensor function has been identified\",\n        \"The signal transduction pathway from host contact to exocytosis is uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"apical exocytic site (rhoptry secretion site)\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"rhoptry secretion / host cell invasion\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"CRMP complex (CRMPA, CRMPB, MIC15, TSP1)\"],\n    \"partners\": [\"CRMPA (TGGT1_261080)\", \"MIC15\", \"TSP1 (thrombospondin type 1 domain-containing protein)\"],\n    \"other_free_text\": [\n      \"Membrane-bound, apicomplexan-conserved protein; TGGT1_292020\",\n      \"Not required for assembly of the rhoptry secretion machinery but transiently associates with the exocytic site prior to invasion, consistent with a host-molecular sensor role [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_292020","name":"CRMPB","product":"cysteine repeat modular protein CRMPB","uniprot_acc":"S8G8P0","chromosome":"TGME49_chrIX","start_pos":4477258},{"strain":"GT1","gene_id":"TGGT1_292020","name":"CRMPB","product":"cysteine repeat modular protein CRMPB","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":4285927},{"strain":"RH88","gene_id":"TGRH88_015880","name":null,"product":"GCC2 and GCC3 domain-containing protein","uniprot_acc":null,"chromosome":"CM023090","start_pos":4544282},{"strain":"VEG","gene_id":"TGVEG_292020","name":null,"product":"GCC2 and GCC3 domain-containing protein","uniprot_acc":"B9QEH5","chromosome":"TGVEG_chrIX","start_pos":4515232}]}