{"gene":"TG_207460","gene_symbol":"RAB5B","run_date":"2026-09-08T11:06:18","timeline":{"discoveries":[{"year":2025,"finding":"Rab5b participates in a cycle of endocytosis and exocytosis of the plasma membrane during intracellular replication of Toxoplasma gondii, and this cycle depends on both Rab5b and MyoF. Perturbation of the endo-exocytic balance (involving Rab5b) disrupts plasma membrane reservoir (PMR) formation, leading to increased number and size of PMRs and ultimately a complete loss of membrane organization.","method":"Conditional depletion / genetic perturbation with phenotypic readout (live imaging of membrane dynamics, assessment of PMR formation and size)","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, direct loss-of-function with defined cellular phenotype (PMR disruption), but abstract does not detail orthogonal biochemical validation","pmids":["41026795"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"finding":"Rab5b is dispensable for the lytic cycle of Toxoplasma gondii, in contrast to its ortholog's role in Plasmodium falciparum.","method":"Genetic depletion of Rab5b with assessment of lytic cycle completion","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, direct loss-of-function with clear negative lytic-cycle phenotype, single method reported","pmids":["41026795"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"Toxoplasma gondii Rab5b functions in the endo-exocytic recycling of the parasite plasma membrane during intracellular replication, acting together with MyoF to regulate plasma membrane reservoir (PMR) formation, while being dispensable for the overall lytic cycle."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, Rab5b regulates a cycle of plasma membrane endocytosis and exocytosis during intracellular replication, functioning together with MyoF to control formation of the plasma membrane reservoir (PMR) [PMID:41026795]. Genetic perturbation of the Rab5b-dependent endo-exocytic balance disrupts PMR formation, producing increased number and size of PMRs and ultimately a complete loss of membrane organization [PMID:41026795]. Despite this membrane-organizing role, Rab5b is dispensable for completion of the parasite's lytic cycle, in contrast to its ortholog in Plasmodium falciparum [PMID:41026795]. Beyond these findings, no further biochemical mechanism, effector, or interaction detail for Rab5b has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether a Rab5-family GTPase governs plasma membrane turnover during Toxoplasma replication was unresolved; conditional perturbation established that Rab5b drives an endo-exocytic membrane cycle required for proper plasma membrane reservoir formation together with MyoF.","evidence":"Conditional depletion/genetic perturbation with live imaging of membrane dynamics and assessment of PMR number and size in Toxoplasma gondii","pmids":["41026795"],"confidence":"Medium","gaps":["No orthogonal biochemical validation of the Rab5b-MyoF functional relationship reported","Direct effectors, GEFs/GAPs, or membrane-recruitment mechanism of Rab5b not identified","Molecular basis linking Rab5b activity to PMR size control not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"claim":"Whether Rab5b is essential for the parasite's replicative lytic cycle was untested; genetic depletion showed it is dispensable, distinguishing Toxoplasma Rab5b from the essential Plasmodium falciparum ortholog.","evidence":"Genetic depletion of Rab5b with assessment of lytic cycle completion in Toxoplasma gondii","pmids":["41026795"],"confidence":"Medium","gaps":["Single method (depletion) reported without complementation/rescue","Basis for the divergence in essentiality between Toxoplasma and Plasmodium orthologs not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular effectors, regulatory GTPase cycle, and membrane-trafficking pathway through which Rab5b controls PMR dynamics remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No Rab5b effectors or interaction partners identified beyond a functional link to MyoF","Mechanism of Rab5b recruitment to the plasma membrane not characterized","No structural or biochemical characterization of Rab5b GTPase activity"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MYOF (FUNCTIONAL COOPERATION IN PLASMA MEMBRANE ENDO-EXOCYTIC CYCLE AND PMR FORMATION) [#0]"],"other_free_text":["Rab5b controls formation of the plasma membrane reservoir (PMR); perturbation increases PMR number and size and causes loss of membrane organization [#0]","Rab5b is dispensable for the Toxoplasma gondii lytic cycle, unlike its essential Plasmodium falciparum ortholog [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"41026795","id":"PMC_41026795","title":"Plasma membrane recycling drives reservoir formation during Toxoplasma gondii intracellular replication.","date":"2025","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/41026795","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2966,"output_tokens":571,"usd":0.008731,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5262,"output_tokens":1542,"usd":0.03243,"stage2_stop_reason":"end_turn"},"total_usd":0.041161,"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\": \"Rab5b participates in a cycle of endocytosis and exocytosis of the plasma membrane during intracellular replication of Toxoplasma gondii, and this cycle depends on both Rab5b and MyoF. Perturbation of the endo-exocytic balance (involving Rab5b) disrupts plasma membrane reservoir (PMR) formation, leading to increased number and size of PMRs and ultimately a complete loss of membrane organization.\",\n      \"method\": \"Conditional depletion / genetic perturbation with phenotypic readout (live imaging of membrane dynamics, assessment of PMR formation and size)\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, direct loss-of-function with defined cellular phenotype (PMR disruption), but abstract does not detail orthogonal biochemical validation\",\n      \"pmids\": [\"41026795\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Rab5b is dispensable for the lytic cycle of Toxoplasma gondii, in contrast to its ortholog's role in Plasmodium falciparum.\",\n      \"method\": \"Genetic depletion of Rab5b with assessment of lytic cycle completion\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, direct loss-of-function with clear negative lytic-cycle phenotype, single method reported\",\n      \"pmids\": [\"41026795\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"Toxoplasma gondii Rab5b functions in the endo-exocytic recycling of the parasite plasma membrane during intracellular replication, acting together with MyoF to regulate plasma membrane reservoir (PMR) formation, while being dispensable for the overall lytic cycle.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, Rab5b regulates a cycle of plasma membrane endocytosis and exocytosis during intracellular replication, functioning together with MyoF to control formation of the plasma membrane reservoir (PMR) [#0]. Genetic perturbation of the Rab5b-dependent endo-exocytic balance disrupts PMR formation, producing increased number and size of PMRs and ultimately a complete loss of membrane organization [#0]. Despite this membrane-organizing role, Rab5b is dispensable for completion of the parasite's lytic cycle, in contrast to its ortholog in Plasmodium falciparum [#1]. Beyond these findings, no further biochemical mechanism, effector, or interaction detail for Rab5b has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether a Rab5-family GTPase governs plasma membrane turnover during Toxoplasma replication was unresolved; conditional perturbation established that Rab5b drives an endo-exocytic membrane cycle required for proper plasma membrane reservoir formation together with MyoF.\",\n      \"evidence\": \"Conditional depletion/genetic perturbation with live imaging of membrane dynamics and assessment of PMR number and size in Toxoplasma gondii\",\n      \"pmids\": [\"41026795\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No orthogonal biochemical validation of the Rab5b-MyoF functional relationship reported\",\n        \"Direct effectors, GEFs/GAPs, or membrane-recruitment mechanism of Rab5b not identified\",\n        \"Molecular basis linking Rab5b activity to PMR size control not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether Rab5b is essential for the parasite's replicative lytic cycle was untested; genetic depletion showed it is dispensable, distinguishing Toxoplasma Rab5b from the essential Plasmodium falciparum ortholog.\",\n      \"evidence\": \"Genetic depletion of Rab5b with assessment of lytic cycle completion in Toxoplasma gondii\",\n      \"pmids\": [\"41026795\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method (depletion) reported without complementation/rescue\",\n        \"Basis for the divergence in essentiality between Toxoplasma and Plasmodium orthologs not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular effectors, regulatory GTPase cycle, and membrane-trafficking pathway through which Rab5b controls PMR dynamics remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No Rab5b effectors or interaction partners identified beyond a functional link to MyoF\",\n        \"Mechanism of Rab5b recruitment to the plasma membrane not characterized\",\n        \"No structural or biochemical characterization of Rab5b GTPase activity\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006897\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006887\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MyoF (functional cooperation in plasma membrane endo-exocytic cycle and PMR formation) [#0]\"],\n    \"other_free_text\": [\n      \"Rab5b controls formation of the plasma membrane reservoir (PMR); perturbation increases PMR number and size and causes loss of membrane organization [#0]\",\n      \"Rab5b is dispensable for the Toxoplasma gondii lytic cycle, unlike its essential Plasmodium falciparum ortholog [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_207460","name":"RAB5B","product":"ras-related protein RAB5B","uniprot_acc":"A0A125YXV4","chromosome":"TGME49_chrIb","start_pos":75943},{"strain":"GT1","gene_id":"TGGT1_207460B","name":null,"product":"Rab5B protein","uniprot_acc":null,"chromosome":"TGGT1_chrIb","start_pos":91448},{"strain":"RH88","gene_id":"TGRH88_023080","name":null,"product":"Rab5B protein","uniprot_acc":null,"chromosome":"CM023082","start_pos":1930905},{"strain":"VEG","gene_id":"TGVEG_207460B","name":null,"product":"Rab5B protein","uniprot_acc":"A0A125YUM5","chromosome":"TGVEG_chrIb","start_pos":73328}]}