{"gene":"TG_271060","gene_symbol":"VPS45","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2019,"finding":"TgVps45 interacts with SNARE proteins TgStx16 and TgVAMP4-1, forming a complex involved in vesicle fusion at the trans-Golgi network (TGN).","method":"Co-immunoprecipitation / protein interaction assay","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP identifying binding partners, supported by genetic epistasis (conditional ablation of TgStx16 phenocopies TgVps45 deficiency), single lab","pmids":["31670849"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"finding":"Conditional depletion of TgVps45 (using auxin-inducible degron) causes morphological changes including asymmetrical loss of the inner membrane complex (IMC), defects in nucleation of sub-pellicular microtubules, impaired polarization, and defective symmetrical assembly of daughter parasites during endodyogeny.","method":"Auxin-inducible degron conditional knockout with phenotypic analysis (microscopy)","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined cellular phenotypes, single lab, multiple morphological readouts","pmids":["31670849"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgVps45 is implicated in the biogenesis of the inner membrane complex (alveoli) in both Toxoplasma gondii and Plasmodium falciparum, likely acting in a coordinated manner with Stx16 and Stx6, and plays a critical role in trafficking of endocytosed host proteins.","method":"Conditional knockdown / genetic depletion with phenotypic and trafficking analysis; comparative study across two apicomplexan species","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional depletion with defined organellar phenotypes replicated across two species (T. gondii and P. falciparum), single study","pmids":["33082261"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"TgVps45 is a Sec1/Munc18-like protein that functions at the trans-Golgi network by interacting with SNARE proteins TgStx16 and TgVAMP4-1 to mediate vesicle fusion, and is required for inner membrane complex (alveoli) biogenesis, sub-pellicular microtubule nucleation, polarized assembly of daughter parasites during endodyogeny, and trafficking of endocytosed host proteins."},"narrative":{"mechanistic_narrative":"VPS45 (TgVps45) is a Sec1/Munc18-like regulator of vesicle fusion that operates at the trans-Golgi network in apicomplexan parasites, where it acts through the SNARE machinery to support membrane trafficking and biogenesis of the parasite pellicle [PMID:31670849]. It interacts with the SNARE proteins TgStx16 and TgVAMP4-1 to form a fusion complex, with conditional ablation of TgStx16 phenocopying TgVps45 deficiency and thereby placing the two in a common pathway [PMID:31670849]. Conditional depletion of TgVps45 disrupts inner membrane complex (alveoli) formation, sub-pellicular microtubule nucleation, cell polarization, and the symmetrical assembly of daughter parasites during endodyogeny [PMID:31670849]. A role in IMC biogenesis and in trafficking of endocytosed host proteins is conserved across Toxoplasma gondii and Plasmodium falciparum, where TgVps45 acts coordinately with Stx16 and Stx6 [PMID:33082261]. Beyond these SNARE interactions and trafficking phenotypes, no further biochemical detail of the fusion mechanism has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Establishing the binding partners of TgVps45 was needed to place it in a defined membrane-fusion pathway; identifying its SNARE partners located its action at the trans-Golgi network.","evidence":"Co-immunoprecipitation identifying TgStx16 and TgVAMP4-1, supported by genetic epistasis via conditional TgStx16 ablation, in Toxoplasma gondii","pmids":["31670849"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation or reconstitution of the fusion complex","Direct SM-protein/SNARE binding mode and stoichiometry not defined","TGN localization inferred rather than mapped biochemically"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2019,"claim":"Whether TgVps45 has a cell-biological role beyond generic vesicle fusion was unknown; conditional depletion revealed it is required for pellicle and cytoskeletal morphogenesis during division.","evidence":"Auxin-inducible degron conditional knockout with microscopy readouts of IMC, microtubules, polarization, and endodyogeny in Toxoplasma gondii","pmids":["31670849"],"confidence":"Medium","gaps":["Molecular link between vesicle fusion and IMC/microtubule assembly not resolved","Cargo delivered by the TgVps45-dependent route not identified","Single lab, single species"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Whether the TgVps45 trafficking function is conserved and what cargo it handles was open; comparative depletion showed a conserved role in alveoli biogenesis and in trafficking of endocytosed host proteins across two apicomplexans.","evidence":"Conditional knockdown/genetic depletion with organellar and trafficking phenotyping in Toxoplasma gondii and Plasmodium falciparum","pmids":["33082261"],"confidence":"Medium","gaps":["Coordinated action with Stx16 and Stx6 stated as likely but not biochemically dissected","Mechanism connecting host-protein endocytosis to IMC biogenesis unresolved","Direct fusion assay for the endocytic route absent"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How TgVps45-mediated vesicle fusion is mechanistically coupled to inner membrane complex biogenesis, microtubule nucleation, and host-protein endocytosis remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the TgVps45-SNARE complex","Full SNARE partner set and directionality of fusion not defined","Cargo identity for the endocytic trafficking route not established"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TgVps45-TgStx16-TgVAMP4-1 SNARE fusion complex (TGN)"],"partners":["TGSTX16 (SNARE)","TGVAMP4-1 (SNARE)","STX6 (COORDINATED ACTION, INFERRED)"],"other_free_text":["Required for inner membrane complex (alveoli) biogenesis and sub-pellicular microtubule nucleation [#1, #2]","Required for polarized, symmetrical daughter-cell assembly during endodyogeny [#1]","Function in IMC biogenesis and host-protein trafficking conserved between Toxoplasma gondii and Plasmodium falciparum [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"33082261","id":"PMC_33082261","title":"The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/33082261","citation_count":32,"is_preprint":false},{"pmid":"31670849","id":"PMC_31670849","title":"The Sec1/Munc18-like proteins TgSec1 and TgVps45 play pivotal roles in assembly of the pellicle and sub-pellicle network in Toxoplasma gondii.","date":"2019","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31670849","citation_count":12,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3629,"output_tokens":849,"usd":0.011811,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5656,"output_tokens":2225,"usd":0.041952,"stage2_stop_reason":"end_turn"},"total_usd":0.053763,"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\": 2019,\n      \"finding\": \"TgVps45 interacts with SNARE proteins TgStx16 and TgVAMP4-1, forming a complex involved in vesicle fusion at the trans-Golgi network (TGN).\",\n      \"method\": \"Co-immunoprecipitation / protein interaction assay\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP identifying binding partners, supported by genetic epistasis (conditional ablation of TgStx16 phenocopies TgVps45 deficiency), single lab\",\n      \"pmids\": [\"31670849\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Conditional depletion of TgVps45 (using auxin-inducible degron) causes morphological changes including asymmetrical loss of the inner membrane complex (IMC), defects in nucleation of sub-pellicular microtubules, impaired polarization, and defective symmetrical assembly of daughter parasites during endodyogeny.\",\n      \"method\": \"Auxin-inducible degron conditional knockout with phenotypic analysis (microscopy)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined cellular phenotypes, single lab, multiple morphological readouts\",\n      \"pmids\": [\"31670849\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgVps45 is implicated in the biogenesis of the inner membrane complex (alveoli) in both Toxoplasma gondii and Plasmodium falciparum, likely acting in a coordinated manner with Stx16 and Stx6, and plays a critical role in trafficking of endocytosed host proteins.\",\n      \"method\": \"Conditional knockdown / genetic depletion with phenotypic and trafficking analysis; comparative study across two apicomplexan species\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional depletion with defined organellar phenotypes replicated across two species (T. gondii and P. falciparum), single study\",\n      \"pmids\": [\"33082261\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgVps45 is a Sec1/Munc18-like protein that functions at the trans-Golgi network by interacting with SNARE proteins TgStx16 and TgVAMP4-1 to mediate vesicle fusion, and is required for inner membrane complex (alveoli) biogenesis, sub-pellicular microtubule nucleation, polarized assembly of daughter parasites during endodyogeny, and trafficking of endocytosed host proteins.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"VPS45 (TgVps45) is a Sec1/Munc18-like regulator of vesicle fusion that operates at the trans-Golgi network in apicomplexan parasites, where it acts through the SNARE machinery to support membrane trafficking and biogenesis of the parasite pellicle [#0, #1]. It interacts with the SNARE proteins TgStx16 and TgVAMP4-1 to form a fusion complex, with conditional ablation of TgStx16 phenocopying TgVps45 deficiency and thereby placing the two in a common pathway [#0]. Conditional depletion of TgVps45 disrupts inner membrane complex (alveoli) formation, sub-pellicular microtubule nucleation, cell polarization, and the symmetrical assembly of daughter parasites during endodyogeny [#1]. A role in IMC biogenesis and in trafficking of endocytosed host proteins is conserved across Toxoplasma gondii and Plasmodium falciparum, where TgVps45 acts coordinately with Stx16 and Stx6 [#2]. Beyond these SNARE interactions and trafficking phenotypes, no further biochemical detail of the fusion mechanism has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing the binding partners of TgVps45 was needed to place it in a defined membrane-fusion pathway; identifying its SNARE partners located its action at the trans-Golgi network.\",\n      \"evidence\": \"Co-immunoprecipitation identifying TgStx16 and TgVAMP4-1, supported by genetic epistasis via conditional TgStx16 ablation, in Toxoplasma gondii\",\n      \"pmids\": [\"31670849\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation or reconstitution of the fusion complex\",\n        \"Direct SM-protein/SNARE binding mode and stoichiometry not defined\",\n        \"TGN localization inferred rather than mapped biochemically\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Whether TgVps45 has a cell-biological role beyond generic vesicle fusion was unknown; conditional depletion revealed it is required for pellicle and cytoskeletal morphogenesis during division.\",\n      \"evidence\": \"Auxin-inducible degron conditional knockout with microscopy readouts of IMC, microtubules, polarization, and endodyogeny in Toxoplasma gondii\",\n      \"pmids\": [\"31670849\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular link between vesicle fusion and IMC/microtubule assembly not resolved\",\n        \"Cargo delivered by the TgVps45-dependent route not identified\",\n        \"Single lab, single species\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether the TgVps45 trafficking function is conserved and what cargo it handles was open; comparative depletion showed a conserved role in alveoli biogenesis and in trafficking of endocytosed host proteins across two apicomplexans.\",\n      \"evidence\": \"Conditional knockdown/genetic depletion with organellar and trafficking phenotyping in Toxoplasma gondii and Plasmodium falciparum\",\n      \"pmids\": [\"33082261\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Coordinated action with Stx16 and Stx6 stated as likely but not biochemically dissected\",\n        \"Mechanism connecting host-protein endocytosis to IMC biogenesis unresolved\",\n        \"Direct fusion assay for the endocytic route absent\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgVps45-mediated vesicle fusion is mechanistically coupled to inner membrane complex biogenesis, microtubule nucleation, and host-protein endocytosis remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of the TgVps45-SNARE complex\",\n        \"Full SNARE partner set and directionality of fusion not defined\",\n        \"Cargo identity for the endocytic trafficking route not established\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019905\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005802\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006906\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006897\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"TgVps45-TgStx16-TgVAMP4-1 SNARE fusion complex (TGN)\"\n    ],\n    \"partners\": [\n      \"TgStx16 (SNARE)\",\n      \"TgVAMP4-1 (SNARE)\",\n      \"Stx6 (coordinated action, inferred)\"\n    ],\n    \"other_free_text\": [\n      \"Required for inner membrane complex (alveoli) biogenesis and sub-pellicular microtubule nucleation [#1, #2]\",\n      \"Required for polarized, symmetrical daughter-cell assembly during endodyogeny [#1]\",\n      \"Function in IMC biogenesis and host-protein trafficking conserved between Toxoplasma gondii and Plasmodium falciparum [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_271060","name":"VPS45","product":"vacuolar protein sorting-associated protein 45","uniprot_acc":"A0A125YXG7","chromosome":"TGME49_chrVIII","start_pos":4745377},{"strain":"GT1","gene_id":"TGGT1_271060","name":null,"product":"Sec1 family protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":4742620},{"strain":"RH88","gene_id":"TGRH88_080360","name":null,"product":"Sec1 family protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":9863385},{"strain":"VEG","gene_id":"TGVEG_271060","name":null,"product":"Sec1 family protein","uniprot_acc":"B9PI32","chromosome":"TGVEG_chrVIII","start_pos":4758626}]}