{"gene":"TG_257370","gene_symbol":"PCR2","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2022,"finding":"Pcr2 (Preconoidal region protein 2) localizes to the apical complex and is required for persistent (non-spasmodic) gliding motility; knockout parasites show spasmodic movement despite largely unperturbed actomyosin activity (as indicated by actin chromobody motion), placing Pcr2 downstream of or in parallel with the actomyosin machinery.","method":"Knockout (KO) generation, calcium-induced egress assays, live motility imaging with mEmerald-tagged actin chromobody, invasion and egress phenotypic readouts","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype and multiple orthogonal assays (motility, invasion, egress, actin dynamics) in a single lab","pmids":["35994509"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Pcr2 KO parasites are impaired in assembling the moving junction, contributing to defective invasion in addition to faulty motility.","method":"Knockout (KO) generation, invasion assays, moving junction formation assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype (moving junction assembly defect) alongside motility phenotype, single lab","pmids":["35994509"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Calcium-induced secretion of the major adhesin MIC2 appears normal in Pcr2 KO parasites, indicating Pcr2 acts downstream of adhesin secretion in the motility/invasion pathway.","method":"Calcium-induced egress stimulation, MIC2 secretion assay in KO parasites","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO with specific secretion readout, single lab, single method for this sub-finding","pmids":["35994509"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Ultrastructure expansion microscopy established that Preconoidal Rings (PCRs), which include Pcr2 as a component, serve as a hub for glideosome components including Formin1, linking the PCR structure to glideosome assembly and motility.","method":"Ultrastructure expansion microscopy (U-ExM), localization of glideosome components relative to PCR markers","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — high-resolution structural imaging with functional context, single lab; Pcr2 specifically is mentioned as a PCR component implicitly via the broader PCR characterization","pmids":["36109645"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"Pcr2 is a component of the preconoidal rings (PCRs) at the apical complex of Toxoplasma gondii that is required for persistent gliding motility and moving junction assembly during invasion and egress, acting downstream of or in parallel with the actomyosin machinery and downstream of MIC2 adhesin secretion, while the PCR structure as a whole serves as a hub for glideosome assembly including Formin1 recruitment."},"narrative":{"mechanistic_narrative":"Pcr2 is a component of the preconoidal rings (PCRs) at the apical complex of Toxoplasma gondii that couples apical structural organization to the parasite's invasive machinery [PMID:35994509, PMID:36109645]. Genetic ablation of Pcr2 converts normal persistent gliding into spasmodic movement while leaving actomyosin activity (actin chromobody motion) largely intact, placing Pcr2 downstream of or in parallel with the actomyosin motor [PMID:35994509]. Beyond motility, Pcr2 knockout parasites fail to properly assemble the moving junction, contributing to defective host-cell invasion [PMID:35994509]. Because calcium-induced secretion of the major adhesin MIC2 is unperturbed in the knockout, Pcr2 acts downstream of adhesin secretion in the motility and invasion pathway [PMID:35994509]. At the structural level, the PCRs that contain Pcr2 serve as a hub for glideosome components including Formin1, linking this apical ring to glideosome assembly [PMID:36109645]. No direct biochemical activity, binding partners, or structural model for Pcr2 itself have been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Establishing where Pcr2 acts in the motility pathway was unknown; showing that knockout parasites glide spasmodically despite intact actin dynamics placed Pcr2 downstream of or in parallel with the actomyosin machinery rather than as part of the motor itself.","evidence":"Knockout generation with calcium-induced egress and live motility imaging using an mEmerald-tagged actin chromobody","pmids":["35994509"],"confidence":"Medium","gaps":["Molecular mechanism linking Pcr2 to persistent versus spasmodic gliding not defined","No direct binding partners identified","Whether Pcr2 acts on the motor or on force transmission unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Whether Pcr2's role extended to host-cell entry was unknown; the knockout's failure to assemble the moving junction demonstrated an invasion defect distinct from the motility phenotype.","evidence":"Knockout invasion assays and moving junction formation assays","pmids":["35994509"],"confidence":"Medium","gaps":["Mechanism by which Pcr2 promotes moving junction assembly unknown","No identified moving junction component interacting with Pcr2"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"The step at which Pcr2 acts relative to adhesin release was unclear; normal calcium-induced MIC2 secretion in the knockout placed Pcr2 downstream of adhesin secretion.","evidence":"Calcium-induced MIC2 secretion assay in knockout parasites","pmids":["35994509"],"confidence":"Medium","gaps":["Only MIC2 tested; other secreted effectors not assessed","Single method for this sub-finding"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"How the PCR structure containing Pcr2 relates to the glideosome was unknown; high-resolution imaging established the PCRs as a hub for glideosome components including Formin1.","evidence":"Ultrastructure expansion microscopy (U-ExM) localizing glideosome components relative to PCR markers","pmids":["36109645"],"confidence":"Medium","gaps":["Pcr2 implicated only via broader PCR characterization, not directly resolved","Direct interaction between Pcr2 and Formin1 not shown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical function of Pcr2, its direct binding partners, and its structural role within the preconoidal rings remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No molecular activity assigned to Pcr2","No direct interactome or structural model","Mechanistic link between PCR integrity and persistent gliding unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Preconoidal rings (PCRs)"],"partners":[],"other_free_text":["Pcr2 acts downstream of MIC2 adhesin secretion and downstream of or in parallel with the actomyosin machinery [#0, #2].","PCRs containing Pcr2 serve as a hub for glideosome components including Formin1 [#3]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"36109645","id":"PMC_36109645","title":"Conoid extrusion regulates glideosome assembly to control motility and invasion in Apicomplexa.","date":"2022","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/36109645","citation_count":37,"is_preprint":false},{"pmid":"35994509","id":"PMC_35994509","title":"An apical protein, Pcr2, is required for persistent movement by the human parasite Toxoplasma gondii.","date":"2022","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/35994509","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3408,"output_tokens":1050,"usd":0.012987,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5929,"output_tokens":2119,"usd":0.04131,"stage2_stop_reason":"end_turn"},"total_usd":0.054297,"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\": \"Pcr2 (Preconoidal region protein 2) localizes to the apical complex and is required for persistent (non-spasmodic) gliding motility; knockout parasites show spasmodic movement despite largely unperturbed actomyosin activity (as indicated by actin chromobody motion), placing Pcr2 downstream of or in parallel with the actomyosin machinery.\",\n      \"method\": \"Knockout (KO) generation, calcium-induced egress assays, live motility imaging with mEmerald-tagged actin chromobody, invasion and egress phenotypic readouts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype and multiple orthogonal assays (motility, invasion, egress, actin dynamics) in a single lab\",\n      \"pmids\": [\"35994509\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Pcr2 KO parasites are impaired in assembling the moving junction, contributing to defective invasion in addition to faulty motility.\",\n      \"method\": \"Knockout (KO) generation, invasion assays, moving junction formation assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype (moving junction assembly defect) alongside motility phenotype, single lab\",\n      \"pmids\": [\"35994509\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Calcium-induced secretion of the major adhesin MIC2 appears normal in Pcr2 KO parasites, indicating Pcr2 acts downstream of adhesin secretion in the motility/invasion pathway.\",\n      \"method\": \"Calcium-induced egress stimulation, MIC2 secretion assay in KO parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO with specific secretion readout, single lab, single method for this sub-finding\",\n      \"pmids\": [\"35994509\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Ultrastructure expansion microscopy established that Preconoidal Rings (PCRs), which include Pcr2 as a component, serve as a hub for glideosome components including Formin1, linking the PCR structure to glideosome assembly and motility.\",\n      \"method\": \"Ultrastructure expansion microscopy (U-ExM), localization of glideosome components relative to PCR markers\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — high-resolution structural imaging with functional context, single lab; Pcr2 specifically is mentioned as a PCR component implicitly via the broader PCR characterization\",\n      \"pmids\": [\"36109645\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"Pcr2 is a component of the preconoidal rings (PCRs) at the apical complex of Toxoplasma gondii that is required for persistent gliding motility and moving junction assembly during invasion and egress, acting downstream of or in parallel with the actomyosin machinery and downstream of MIC2 adhesin secretion, while the PCR structure as a whole serves as a hub for glideosome assembly including Formin1 recruitment.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Pcr2 is a component of the preconoidal rings (PCRs) at the apical complex of Toxoplasma gondii that couples apical structural organization to the parasite's invasive machinery [#0, #3]. Genetic ablation of Pcr2 converts normal persistent gliding into spasmodic movement while leaving actomyosin activity (actin chromobody motion) largely intact, placing Pcr2 downstream of or in parallel with the actomyosin motor [#0]. Beyond motility, Pcr2 knockout parasites fail to properly assemble the moving junction, contributing to defective host-cell invasion [#1]. Because calcium-induced secretion of the major adhesin MIC2 is unperturbed in the knockout, Pcr2 acts downstream of adhesin secretion in the motility and invasion pathway [#2]. At the structural level, the PCRs that contain Pcr2 serve as a hub for glideosome components including Formin1, linking this apical ring to glideosome assembly [#3]. No direct biochemical activity, binding partners, or structural model for Pcr2 itself have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing where Pcr2 acts in the motility pathway was unknown; showing that knockout parasites glide spasmodically despite intact actin dynamics placed Pcr2 downstream of or in parallel with the actomyosin machinery rather than as part of the motor itself.\",\n      \"evidence\": \"Knockout generation with calcium-induced egress and live motility imaging using an mEmerald-tagged actin chromobody\",\n      \"pmids\": [\"35994509\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism linking Pcr2 to persistent versus spasmodic gliding not defined\", \"No direct binding partners identified\", \"Whether Pcr2 acts on the motor or on force transmission unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether Pcr2's role extended to host-cell entry was unknown; the knockout's failure to assemble the moving junction demonstrated an invasion defect distinct from the motility phenotype.\",\n      \"evidence\": \"Knockout invasion assays and moving junction formation assays\",\n      \"pmids\": [\"35994509\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which Pcr2 promotes moving junction assembly unknown\", \"No identified moving junction component interacting with Pcr2\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The step at which Pcr2 acts relative to adhesin release was unclear; normal calcium-induced MIC2 secretion in the knockout placed Pcr2 downstream of adhesin secretion.\",\n      \"evidence\": \"Calcium-induced MIC2 secretion assay in knockout parasites\",\n      \"pmids\": [\"35994509\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Only MIC2 tested; other secreted effectors not assessed\", \"Single method for this sub-finding\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"How the PCR structure containing Pcr2 relates to the glideosome was unknown; high-resolution imaging established the PCRs as a hub for glideosome components including Formin1.\",\n      \"evidence\": \"Ultrastructure expansion microscopy (U-ExM) localizing glideosome components relative to PCR markers\",\n      \"pmids\": [\"36109645\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Pcr2 implicated only via broader PCR characterization, not directly resolved\", \"Direct interaction between Pcr2 and Formin1 not shown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical function of Pcr2, its direct binding partners, and its structural role within the preconoidal rings remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular activity assigned to Pcr2\", \"No direct interactome or structural model\", \"Mechanistic link between PCR integrity and persistent gliding unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"apical complex\", \"supporting_discovery_ids\": [0, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"preconoidal rings\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"gliding motility\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"host cell invasion / moving junction assembly\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"glideosome assembly\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Preconoidal rings (PCRs)\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Pcr2 acts downstream of MIC2 adhesin secretion and downstream of or in parallel with the actomyosin machinery [#0, #2].\",\n      \"PCRs containing Pcr2 serve as a hub for glideosome components including Formin1 [#3].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_257370","name":"PCR2","product":"preconoidal region protein PCR2","uniprot_acc":"A0A125YUP8","chromosome":"TGME49_chrVIIb","start_pos":4086320},{"strain":"GT1","gene_id":"TGGT1_257370","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":4019662},{"strain":"RH88","gene_id":"TGRH88_072500","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":4121242},{"strain":"VEG","gene_id":"TGVEG_257370","name":null,"product":"hypothetical protein","uniprot_acc":"B6KAY9","chromosome":"TGVEG_chrVIIb","start_pos":4104807}]}