{"gene":"TG_208420","gene_symbol":"SLF","run_date":"2026-09-08T11:06:19","timeline":{"discoveries":[{"year":2022,"finding":"SLF (signalling linking factor) is an integral part of a signalling complex required for early induction of egress in Toxoplasma gondii, as demonstrated by conditional knockout parasites (DiCre-system) showing defects at an early egress step, with F-actin dynamics and apicoplast segregation used as phenotypic indicators.","method":"Conditional knockout (DiCre system), splitCas9 phenotypic screen, F-actin/apicoplast indicator strain","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined cellular phenotype (early egress block), single lab, two orthogonal methods (screen + DiCre KO)","pmids":["35538310"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"SLF is a novel component of the guanylate cyclase (GC) complex in Toxoplasma gondii; conditional depletion of SLF in tachyzoites impairs microneme exocytosis, conoid extrusion, and motility, preventing invasion and egress, placing SLF functionally within the cGMP-dependent signalling pathway alongside GC, CDC50.1, and UGO.","method":"Conditional depletion (stage-specific promoter swap / inducible knockdown), microneme exocytosis assay, conoid extrusion assay, motility assay, invasion/egress assays","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal functional assays (exocytosis, conoid extrusion, motility, invasion, egress) in a single rigorous study with conditional depletion, pathway placement within the GC complex established","pmids":["36200777"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"SLF-deficient bradyzoites show reduced cyst burden during the onset of chronic infection, and SLF-deficient cysts fail to establish infection upon oral challenge in mice, demonstrating SLF's role in the natural transmission route via the GC signalling complex in the bradyzoite stage.","method":"Stage-specific promoter swap generating SLF-deficient bradyzoites, oral infection mouse model, cyst burden quantification","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo oral infection model with conditional stage-specific depletion, single lab, multiple readouts (cyst burden, infection establishment)","pmids":["36200777"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"SLF (signalling linking factor) is a component of the guanylate cyclase (GC) signalling complex in Toxoplasma gondii that is required for cGMP-dependent early induction of egress; its depletion blocks microneme exocytosis, conoid extrusion, and gliding motility in tachyzoites, and SLF-deficient bradyzoites cannot establish infection via the oral route, indicating an essential role in both acute and chronic stages of the parasite life cycle."},"narrative":{"mechanistic_narrative":"SLF (signalling linking factor) is a component of the guanylate cyclase (GC) signalling complex in Toxoplasma gondii that couples cGMP-dependent signalling to the early induction of egress and the invasion machinery [PMID:35538310, PMID:36200777]. In tachyzoites, SLF functions within the GC complex alongside GC, CDC50.1, and UGO, and its conditional depletion impairs microneme exocytosis, conoid extrusion, and gliding motility, thereby blocking both invasion and egress [PMID:36200777]. SLF activity is also required across the parasite life cycle: SLF-deficient bradyzoites produce reduced cyst burdens and fail to establish infection upon oral challenge, implicating SLF in the natural transmission route [PMID:36200777]. Beyond its placement within the GC complex and these loss-of-function phenotypes, the biochemical basis of SLF's contribution to the complex has not been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Establishing which factors control the timing of egress, SLF was identified as an integral part of a signalling complex required for the early induction of egress, defining a discrete step where its loss arrests the process.","evidence":"SplitCas9 phenotypic screen and DiCre conditional knockout with F-actin/apicoplast indicator strain in T. gondii","pmids":["35538310"],"confidence":"Medium","gaps":["The molecular activity of SLF and its direct binding partners were not defined","The specific early egress signalling step blocked was inferred from indicator phenotypes rather than direct biochemistry"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"To place SLF mechanistically, conditional depletion showed it acts within the cGMP-dependent GC complex, and that its loss simultaneously disrupts microneme exocytosis, conoid extrusion, and motility — linking a single factor to the coordinated invasion/egress program.","evidence":"Conditional depletion via stage-specific promoter swap with microneme exocytosis, conoid extrusion, motility, invasion and egress assays in tachyzoites","pmids":["36200777"],"confidence":"High","gaps":["How SLF physically integrates with GC, CDC50.1, and UGO was not resolved","Whether SLF has enzymatic or purely structural/scaffolding function is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"To test relevance beyond the acute stage, SLF-deficient bradyzoites were shown to be defective in cyst formation and unable to establish oral infection, establishing SLF as essential for the natural transmission route and chronic infection.","evidence":"Stage-specific promoter swap generating SLF-deficient bradyzoites with oral infection mouse model and cyst burden quantification","pmids":["36200777"],"confidence":"Medium","gaps":["The bradyzoite-stage molecular events downstream of SLF were not dissected","Whether the transmission defect reflects the same microneme/motility functions seen in tachyzoites is untested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical function of SLF within the GC complex — its direct interactions, structural role, and how it links cGMP signalling to microneme discharge and conoid extrusion — remains undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure or direct interaction map for SLF within the GC complex","No defined molecular/enzymatic activity for SLF","Mechanism by which SLF couples cGMP signalling to the invasion/egress motor is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Guanylate cyclase (GC) signalling complex (with GC, CDC50.1, UGO)"],"partners":["GC (GUANYLATE CYCLASE)","CDC50.1","UGO"],"other_free_text":["SLF = signalling linking factor, named for its role in the T. gondii GC signalling complex","Depletion phenotypes (microneme exocytosis, conoid extrusion, motility, invasion, egress) all trace to loss-of-function in tachyzoites [#1]","No direct molecular activity or biochemical mechanism for SLF is established in the available corpus"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35538310","id":"PMC_35538310","title":"A splitCas9 phenotypic screen in Toxoplasma gondii identifies proteins involved in host cell egress and invasion.","date":"2022","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35538310","citation_count":35,"is_preprint":false},{"pmid":"36200777","id":"PMC_36200777","title":"A Signaling Factor Linked to Toxoplasma gondii Guanylate Cyclase Complex Controls Invasion and Egress during Acute and Chronic Infection.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/36200777","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3496,"output_tokens":945,"usd":0.012332,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5762,"output_tokens":2097,"usd":0.040618,"stage2_stop_reason":"end_turn"},"total_usd":0.05295,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"SLF (signalling linking factor) is an integral part of a signalling complex required for early induction of egress in Toxoplasma gondii, as demonstrated by conditional knockout parasites (DiCre-system) showing defects at an early egress step, with F-actin dynamics and apicoplast segregation used as phenotypic indicators.\",\n      \"method\": \"Conditional knockout (DiCre system), splitCas9 phenotypic screen, F-actin/apicoplast indicator strain\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined cellular phenotype (early egress block), single lab, two orthogonal methods (screen + DiCre KO)\",\n      \"pmids\": [\"35538310\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SLF is a novel component of the guanylate cyclase (GC) complex in Toxoplasma gondii; conditional depletion of SLF in tachyzoites impairs microneme exocytosis, conoid extrusion, and motility, preventing invasion and egress, placing SLF functionally within the cGMP-dependent signalling pathway alongside GC, CDC50.1, and UGO.\",\n      \"method\": \"Conditional depletion (stage-specific promoter swap / inducible knockdown), microneme exocytosis assay, conoid extrusion assay, motility assay, invasion/egress assays\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal functional assays (exocytosis, conoid extrusion, motility, invasion, egress) in a single rigorous study with conditional depletion, pathway placement within the GC complex established\",\n      \"pmids\": [\"36200777\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SLF-deficient bradyzoites show reduced cyst burden during the onset of chronic infection, and SLF-deficient cysts fail to establish infection upon oral challenge in mice, demonstrating SLF's role in the natural transmission route via the GC signalling complex in the bradyzoite stage.\",\n      \"method\": \"Stage-specific promoter swap generating SLF-deficient bradyzoites, oral infection mouse model, cyst burden quantification\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo oral infection model with conditional stage-specific depletion, single lab, multiple readouts (cyst burden, infection establishment)\",\n      \"pmids\": [\"36200777\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SLF (signalling linking factor) is a component of the guanylate cyclase (GC) signalling complex in Toxoplasma gondii that is required for cGMP-dependent early induction of egress; its depletion blocks microneme exocytosis, conoid extrusion, and gliding motility in tachyzoites, and SLF-deficient bradyzoites cannot establish infection via the oral route, indicating an essential role in both acute and chronic stages of the parasite life cycle.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SLF (signalling linking factor) is a component of the guanylate cyclase (GC) signalling complex in Toxoplasma gondii that couples cGMP-dependent signalling to the early induction of egress and the invasion machinery [#0, #1]. In tachyzoites, SLF functions within the GC complex alongside GC, CDC50.1, and UGO, and its conditional depletion impairs microneme exocytosis, conoid extrusion, and gliding motility, thereby blocking both invasion and egress [#1]. SLF activity is also required across the parasite life cycle: SLF-deficient bradyzoites produce reduced cyst burdens and fail to establish infection upon oral challenge, implicating SLF in the natural transmission route [#2]. Beyond its placement within the GC complex and these loss-of-function phenotypes, the biochemical basis of SLF's contribution to the complex has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing which factors control the timing of egress, SLF was identified as an integral part of a signalling complex required for the early induction of egress, defining a discrete step where its loss arrests the process.\",\n      \"evidence\": \"SplitCas9 phenotypic screen and DiCre conditional knockout with F-actin/apicoplast indicator strain in T. gondii\",\n      \"pmids\": [\"35538310\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular activity of SLF and its direct binding partners were not defined\",\n        \"The specific early egress signalling step blocked was inferred from indicator phenotypes rather than direct biochemistry\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To place SLF mechanistically, conditional depletion showed it acts within the cGMP-dependent GC complex, and that its loss simultaneously disrupts microneme exocytosis, conoid extrusion, and motility — linking a single factor to the coordinated invasion/egress program.\",\n      \"evidence\": \"Conditional depletion via stage-specific promoter swap with microneme exocytosis, conoid extrusion, motility, invasion and egress assays in tachyzoites\",\n      \"pmids\": [\"36200777\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How SLF physically integrates with GC, CDC50.1, and UGO was not resolved\",\n        \"Whether SLF has enzymatic or purely structural/scaffolding function is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To test relevance beyond the acute stage, SLF-deficient bradyzoites were shown to be defective in cyst formation and unable to establish oral infection, establishing SLF as essential for the natural transmission route and chronic infection.\",\n      \"evidence\": \"Stage-specific promoter swap generating SLF-deficient bradyzoites with oral infection mouse model and cyst burden quantification\",\n      \"pmids\": [\"36200777\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The bradyzoite-stage molecular events downstream of SLF were not dissected\",\n        \"Whether the transmission defect reflects the same microneme/motility functions seen in tachyzoites is untested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical function of SLF within the GC complex — its direct interactions, structural role, and how it links cGMP signalling to microneme discharge and conoid extrusion — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structure or direct interaction map for SLF within the GC complex\",\n        \"No defined molecular/enzymatic activity for SLF\",\n        \"Mechanism by which SLF couples cGMP signalling to the invasion/egress motor is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"cGMP-dependent egress signalling (guanylate cyclase complex)\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"microneme exocytosis\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"gliding motility / conoid extrusion\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"host cell invasion and egress\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"bradyzoite cyst formation and oral transmission\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Guanylate cyclase (GC) signalling complex (with GC, CDC50.1, UGO)\"],\n    \"partners\": [\"GC (guanylate cyclase)\", \"CDC50.1\", \"UGO\"],\n    \"other_free_text\": [\n      \"SLF = signalling linking factor, named for its role in the T. gondii GC signalling complex\",\n      \"Depletion phenotypes (microneme exocytosis, conoid extrusion, motility, invasion, egress) all trace to loss-of-function in tachyzoites [#1]\",\n      \"No direct molecular activity or biochemical mechanism for SLF is established in the available corpus\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_208420","name":"SLF","product":"signaling linker factor SLF","uniprot_acc":"A0A125YRX4","chromosome":"TGME49_chrIb","start_pos":690629},{"strain":"GT1","gene_id":"TGGT1_208420","name":null,"product":"Sodium:neurotransmitter symporter family protein","uniprot_acc":null,"chromosome":"TGGT1_chrIb","start_pos":708445},{"strain":"RH88","gene_id":"TGRH88_022440","name":null,"product":"Sodium:neurotransmitter symporter family protein","uniprot_acc":null,"chromosome":"CM023082","start_pos":1308600},{"strain":"VEG","gene_id":"TGVEG_208420","name":null,"product":"Sodium:neurotransmitter symporter family protein","uniprot_acc":"B6KP52","chromosome":"TGVEG_chrIb","start_pos":690412}]}