{"gene":"TG_222200","gene_symbol":"LMBD3","run_date":"2026-09-08T11:06:39","timeline":{"discoveries":[{"year":2025,"finding":"LMBD3 trafficking to the apical annuli is dependent on AAP7: upon AAP7 depletion, LMBD3 fails to reach the annuli and instead accumulates among the secretory organelles, indicating that AAP7 is required for LMBD3 transport to the plasma membrane via a novel trafficking route.","method":"Conditional depletion of AAP7 (ATc-resistant stable parasites) with fluorescence microscopy to track LMBD3 localization","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single-lab conditional knockdown with direct localization readout; preprint, not yet peer-reviewed; single method for the LMBD3-specific finding","pmids":["41256620"],"is_preprint":true,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"finding":"LMBD3 is a plasma membrane-embedded protein that localises to the apical annuli, where it is functionally connected to IMC suture-embedded AAP proteins via AAP7.","method":"Fluorescence microscopy and conditional protein depletion (ATc-resistant stable parasites) placing LMBD3 at the plasma membrane level of the apical annuli","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization inferred from depletion experiment in a preprint; single lab, single method, no direct biochemical validation of plasma membrane embedding","pmids":["41256620"],"is_preprint":true,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"LMBD3 is a plasma membrane protein that localises to the apical annuli of Toxoplasma gondii, and its trafficking to this compartment depends on the novel apical annuli protein AAP7, which bridges plasma membrane-embedded LMBD3 to the IMC suture-embedded AAP proteins."},"narrative":{"mechanistic_narrative":"LMBD3 is a plasma membrane-embedded protein of Toxoplasma gondii that localizes to the apical annuli, structures where the parasite plasma membrane meets the inner membrane complex (IMC) [PMID:41256620]. Its delivery to this compartment depends on the apical annuli protein AAP7: depletion of AAP7 prevents LMBD3 from reaching the annuli and instead causes it to accumulate among the secretory organelles, defining a novel AAP7-dependent trafficking route to the plasma membrane [PMID:41256620]. At the annuli, LMBD3 is functionally connected to the IMC suture-embedded AAP proteins through AAP7, which appears to bridge plasma membrane-embedded LMBD3 to the IMC-embedded AAP scaffold [PMID:41256620]. Beyond this localization and trafficking dependency, no molecular activity, substrate, or downstream function for LMBD3 has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Establishing where LMBD3 resides and how it gets there addressed whether it is an integral apical annuli component and revealed the trafficking machinery required for its delivery.","evidence":"Conditional depletion of AAP7 in ATc-resistant Toxoplasma gondii with fluorescence microscopy tracking LMBD3 localization (preprint)","pmids":["41256620"],"confidence":"Medium","gaps":["The molecular function of LMBD3 at the apical annuli is unknown","Whether LMBD3 directly binds AAP7 or is trafficked via an indirect route was not resolved","Preprint, single lab, single localization method; not independently confirmed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"claim":"Placing LMBD3 at the plasma membrane level of the annuli and linking it to IMC suture-embedded AAP proteins via AAP7 addressed how the two membrane systems at the annuli are physically bridged.","evidence":"Fluorescence microscopy and conditional protein depletion in ATc-resistant Toxoplasma gondii positioning LMBD3 relative to AAP proteins (preprint)","pmids":["41256620"],"confidence":"Low","gaps":["Plasma membrane embedding was inferred from localization, not confirmed biochemically","The direct interaction between LMBD3, AAP7, and the AAP scaffold has not been demonstrated biochemically","The functional consequence of the LMBD3-AAP7-AAP connection is uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular activity of LMBD3 and the biological role of its recruitment to the apical annuli remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No enzymatic or transport activity assigned to LMBD3","No phenotype for LMBD3 loss reported","Mechanism of the AAP7-dependent trafficking route not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["AAP7 (REQUIRED FOR LMBD3 TRAFFICKING TO THE APICAL ANNULI; BRIDGES LMBD3 TO IMC SUTURE-EMBEDDED AAP PROTEINS)"],"other_free_text":["Localizes to the apical annuli of Toxoplasma gondii at the plasma membrane level.","Upon AAP7 depletion, LMBD3 accumulates among secretory organelles instead of reaching the annuli.","All evidence derives from a single preprint using conditional depletion and fluorescence microscopy."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"41256620","id":"PMC_41256620","title":"Toxoplasma gondii AAP7 is essential for functionally connecting the IMC embedded apical annuli to the plasma membrane.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41256620","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3047,"output_tokens":588,"usd":0.008981,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5277,"output_tokens":1682,"usd":0.034217,"stage2_stop_reason":"end_turn"},"total_usd":0.043198,"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\": 2025,\n      \"finding\": \"LMBD3 trafficking to the apical annuli is dependent on AAP7: upon AAP7 depletion, LMBD3 fails to reach the annuli and instead accumulates among the secretory organelles, indicating that AAP7 is required for LMBD3 transport to the plasma membrane via a novel trafficking route.\",\n      \"method\": \"Conditional depletion of AAP7 (ATc-resistant stable parasites) with fluorescence microscopy to track LMBD3 localization\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single-lab conditional knockdown with direct localization readout; preprint, not yet peer-reviewed; single method for the LMBD3-specific finding\",\n      \"pmids\": [\"41256620\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"LMBD3 is a plasma membrane-embedded protein that localises to the apical annuli, where it is functionally connected to IMC suture-embedded AAP proteins via AAP7.\",\n      \"method\": \"Fluorescence microscopy and conditional protein depletion (ATc-resistant stable parasites) placing LMBD3 at the plasma membrane level of the apical annuli\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization inferred from depletion experiment in a preprint; single lab, single method, no direct biochemical validation of plasma membrane embedding\",\n      \"pmids\": [\"41256620\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"LMBD3 is a plasma membrane protein that localises to the apical annuli of Toxoplasma gondii, and its trafficking to this compartment depends on the novel apical annuli protein AAP7, which bridges plasma membrane-embedded LMBD3 to the IMC suture-embedded AAP proteins.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LMBD3 is a plasma membrane-embedded protein of Toxoplasma gondii that localizes to the apical annuli, structures where the parasite plasma membrane meets the inner membrane complex (IMC) [#0, #1]. Its delivery to this compartment depends on the apical annuli protein AAP7: depletion of AAP7 prevents LMBD3 from reaching the annuli and instead causes it to accumulate among the secretory organelles, defining a novel AAP7-dependent trafficking route to the plasma membrane [#0]. At the annuli, LMBD3 is functionally connected to the IMC suture-embedded AAP proteins through AAP7, which appears to bridge plasma membrane-embedded LMBD3 to the IMC-embedded AAP scaffold [#1]. Beyond this localization and trafficking dependency, no molecular activity, substrate, or downstream function for LMBD3 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Establishing where LMBD3 resides and how it gets there addressed whether it is an integral apical annuli component and revealed the trafficking machinery required for its delivery.\",\n      \"evidence\": \"Conditional depletion of AAP7 in ATc-resistant Toxoplasma gondii with fluorescence microscopy tracking LMBD3 localization (preprint)\",\n      \"pmids\": [\n        \"41256620\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular function of LMBD3 at the apical annuli is unknown\",\n        \"Whether LMBD3 directly binds AAP7 or is trafficked via an indirect route was not resolved\",\n        \"Preprint, single lab, single localization method; not independently confirmed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placing LMBD3 at the plasma membrane level of the annuli and linking it to IMC suture-embedded AAP proteins via AAP7 addressed how the two membrane systems at the annuli are physically bridged.\",\n      \"evidence\": \"Fluorescence microscopy and conditional protein depletion in ATc-resistant Toxoplasma gondii positioning LMBD3 relative to AAP proteins (preprint)\",\n      \"pmids\": [\n        \"41256620\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Plasma membrane embedding was inferred from localization, not confirmed biochemically\",\n        \"The direct interaction between LMBD3, AAP7, and the AAP scaffold has not been demonstrated biochemically\",\n        \"The functional consequence of the LMBD3-AAP7-AAP connection is uncharacterized\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity of LMBD3 and the biological role of its recruitment to the apical annuli remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No enzymatic or transport activity assigned to LMBD3\",\n        \"No phenotype for LMBD3 loss reported\",\n        \"Mechanism of the AAP7-dependent trafficking route not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005886\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0015031\",\n        \"supporting_discovery_ids\": [\n          0\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"AAP7 (required for LMBD3 trafficking to the apical annuli; bridges LMBD3 to IMC suture-embedded AAP proteins)\"\n    ],\n    \"other_free_text\": [\n      \"Localizes to the apical annuli of Toxoplasma gondii at the plasma membrane level.\",\n      \"Upon AAP7 depletion, LMBD3 accumulates among secretory organelles instead of reaching the annuli.\",\n      \"All evidence derives from a single preprint using conditional depletion and fluorescence microscopy.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_222200","name":"LMBD3","product":"apical annuli protein LMBD3","uniprot_acc":"S8FE62","chromosome":"TGME49_chrII","start_pos":948735},{"strain":"GT1","gene_id":"TGGT1_222200","name":null,"product":"putative LMBR1 family region protein","uniprot_acc":null,"chromosome":"TGGT1_chrII","start_pos":932475},{"strain":"RH88","gene_id":"TGRH88_001230","name":null,"product":"putative LMBR1 family region protein","uniprot_acc":null,"chromosome":"CM023083","start_pos":1105446},{"strain":"VEG","gene_id":"TGVEG_222200","name":null,"product":"putative LMBR1 family region protein","uniprot_acc":"V4Z3T5","chromosome":"TGVEG_chrII","start_pos":953244}]}