{"gene":"PF3D7_1327300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2023,"finding":"SPM3 (PF3D7_1327300) is a microtubule-associated protein (MAP) conserved within the genus Plasmodium (especially subgenus Laverania) but absent in other Apicomplexa. Conditional knockdown and targeted gene disruption of PfSPM3 in P. falciparum caused severe morphological defects during gametocytogenesis, producing round, non-falciform gametocytes with an aberrant subpellicular microtubule (SPMT) pattern.","method":"Conditional knockdown and targeted gene disruption (loss-of-function), live-cell microscopy, electron microscopy","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined cellular phenotype, corroborated by electron microscopy and replicated across two Plasmodium species in the same study","pmids":["36625655"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Knockout of PbSPM3 in P. berghei (a species with naturally round gametocytes) caused no defect in gametocytogenesis but resulted in aberrant sporozoite motility and a dramatic defect in salivary gland invasion, leading to decreased transmission efficiency. Electron microscopy revealed increased distance between SPMTs and the IMC in PbSPM3-knockout sporozoites compared to wild type, indicating that SPM3 functions to anchor subpellicular microtubules to the inner membrane complex.","method":"Targeted gene knockout, electron microscopy, sporozoite motility assays, mosquito transmission experiments","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype, electron microscopy showing structural dissociation of SPMTs from IMC, functional transmission assay in single rigorous study","pmids":["36625655"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Using PfSPM3 as a BioID bait in P. falciparum gametocytes, proximity-dependent biotinylation identified 37 high-confidence proteins in the immediate vicinity of PfSPM3, constituting its 'proxiome' and representing novel components of the SPMT network in developing gametocytes.","method":"Proximity-dependent biotinylation (BioID) followed by mass spectrometry","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID-MS identifies proximal proteins, single lab, but no reciprocal validation of individual interactions with SPM3 itself beyond spatial proximity","pmids":["41358875"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"SPM3 (PF3D7_1327300) is a Plasmodium-specific subpellicular microtubule-associated protein that anchors subpellicular microtubules (SPMTs) to the inner membrane complex (IMC); its loss in P. falciparum disrupts SPMT organization and blocks falciform gametocyte morphogenesis, while its loss in P. berghei dissociates SPMTs from the IMC in sporozoites and severely impairs motility and salivary gland invasion, collectively establishing SPM3 as an essential structural linker between the SPMT cytoskeleton and the IMC across multiple Plasmodium life-cycle stages."},"narrative":{"mechanistic_narrative":"SPM3 (PF3D7_1327300) is a Plasmodium-specific microtubule-associated protein that functions as a structural linker anchoring subpellicular microtubules (SPMTs) to the inner membrane complex (IMC) across multiple life-cycle stages [PMID:36625655]. It is conserved within the genus Plasmodium (notably subgenus Laverania) but absent from other Apicomplexa [PMID:36625655]. In P. falciparum, conditional knockdown and targeted disruption of SPM3 produce round, non-falciform gametocytes with an aberrant SPMT pattern, establishing a requirement for SPM3 in gametocyte morphogenesis [PMID:36625655]. In P. berghei — which naturally has round gametocytes — SPM3 loss spares gametocytogenesis but causes aberrant sporozoite motility, a severe salivary gland invasion defect, and reduced transmission; electron microscopy shows increased separation between SPMTs and the IMC in knockout sporozoites, directly demonstrating that SPM3 tethers SPMTs to the IMC [PMID:36625655]. Proximity-dependent biotinylation using SPM3 as bait in P. falciparum gametocytes has mapped a 37-protein proxiome representing candidate components of the SPMT network, but individual SPM3 interactions beyond spatial proximity have not been validated in the available corpus [PMID:41358875].","teleology":[{"year":2023,"claim":"Whether a dedicated protein links the subpellicular microtubule cytoskeleton to gametocyte shape was unknown; genetic loss-of-function established SPM3 as required for falciform gametocyte morphogenesis in P. falciparum.","evidence":"Conditional knockdown and targeted gene disruption with live-cell and electron microscopy in P. falciparum","pmids":["36625655"],"confidence":"High","gaps":["Does not define the molecular mechanism by which SPM3 organizes the SPMT pattern","Direct binding partners at the IMC not identified in this study","Whether the morphological defect is a direct or downstream consequence of SPMT disorganization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"It was unclear whether SPM3's role was gametocyte-specific or reflected a general SPMT–IMC anchoring function; knockout in P. berghei showed SPM3 tethers SPMTs to the IMC and is required for sporozoite motility and mosquito transmission.","evidence":"Targeted gene knockout, electron microscopy showing increased SPMT–IMC distance, sporozoite motility assays, and mosquito transmission experiments in P. berghei","pmids":["36625655"],"confidence":"High","gaps":["The molecular interface by which SPM3 bridges SPMTs and the IMC is not defined","Whether SPM3 binds microtubules directly or via intermediary proteins is unresolved","Species divergence: gametocyte morphogenesis phenotype seen in P. falciparum is absent in P. berghei, and the reason is not mechanistically explained"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"The composition of the SPMT network around SPM3 was unknown; BioID mapping in gametocytes identified a proxiome of candidate SPMT-network components.","evidence":"Proximity-dependent biotinylation (BioID) with SPM3 as bait followed by mass spectrometry in P. falciparum gametocytes","pmids":["41358875"],"confidence":"Medium","gaps":["No reciprocal validation of individual SPM3 interactions beyond spatial proximity","Direct binding partners versus mere neighborhood proteins not distinguished","Functional roles of the 37 identified proteins in SPMT anchoring not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The molecular basis of SPM3-mediated SPMT–IMC anchoring — its microtubule-binding and IMC-binding interfaces and its direct partners — remains undetermined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of SPM3 or its binding domains","No validated direct interaction partner at the IMC or on microtubules","Mechanism of SPM3 recruitment and how it enforces SPMT spacing is unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["SPM3 (PF3D7_1327300) anchors subpellicular microtubules to the inner membrane complex; loss increases SPMT–IMC distance in P. berghei sporozoites [#1].","Required for falciform gametocyte morphogenesis and normal SPMT patterning in P. falciparum [#0].","Required for sporozoite motility and salivary gland invasion, and thus mosquito transmission, in P. berghei [#1].","Conserved within genus Plasmodium (notably subgenus Laverania), absent in other Apicomplexa [#0].","BioID proxiome of 37 high-confidence proximal proteins in P. falciparum gametocytes represents candidate SPMT-network components; individual interactions with SPM3 not independently validated [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"36625655","id":"PMC_36625655","title":"A Microtubule-Associated Protein Is Essential for Malaria Parasite Transmission.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/36625655","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM3","PfSPM3","PbSPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41358875","id":"PMC_41358875","title":"An atlas of novel microtubule-associated proteins in the malaria parasite Plasmodium falciparum.","date":"2025","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/41358875","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41716278","id":"","title":"Molecular mechanisms involved in Plasmodium gametocytogenesis.","date":"2026","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41716278","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39915671","id":"","title":"PfFBXO1 is essential for inner membrane complex formation in Plasmodium falciparum during both asexual and transmission stages.","date":"2025","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39915671","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41117539","id":"","title":"Plasmodium berghei IMC1j interacts with δ-tubulin to orchestrate subpellicular microtubule organization in ookinetes.","date":"2025","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/41117539","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41983703","id":"","title":"The cytoskeleton of pathogenic protists.","date":"2026","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/41983703","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32582569","id":"","title":"Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes.","date":"2020","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32582569","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8946,"output_tokens":1018,"usd":0.021054,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5773,"output_tokens":2162,"usd":0.041458,"stage2_stop_reason":"end_turn"},"total_usd":0.062512,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"SPM3 (PF3D7_1327300) is a microtubule-associated protein (MAP) conserved within the genus Plasmodium (especially subgenus Laverania) but absent in other Apicomplexa. Conditional knockdown and targeted gene disruption of PfSPM3 in P. falciparum caused severe morphological defects during gametocytogenesis, producing round, non-falciform gametocytes with an aberrant subpellicular microtubule (SPMT) pattern.\",\n      \"method\": \"Conditional knockdown and targeted gene disruption (loss-of-function), live-cell microscopy, electron microscopy\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined cellular phenotype, corroborated by electron microscopy and replicated across two Plasmodium species in the same study\",\n      \"pmids\": [\"36625655\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Knockout of PbSPM3 in P. berghei (a species with naturally round gametocytes) caused no defect in gametocytogenesis but resulted in aberrant sporozoite motility and a dramatic defect in salivary gland invasion, leading to decreased transmission efficiency. Electron microscopy revealed increased distance between SPMTs and the IMC in PbSPM3-knockout sporozoites compared to wild type, indicating that SPM3 functions to anchor subpellicular microtubules to the inner membrane complex.\",\n      \"method\": \"Targeted gene knockout, electron microscopy, sporozoite motility assays, mosquito transmission experiments\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype, electron microscopy showing structural dissociation of SPMTs from IMC, functional transmission assay in single rigorous study\",\n      \"pmids\": [\"36625655\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Using PfSPM3 as a BioID bait in P. falciparum gametocytes, proximity-dependent biotinylation identified 37 high-confidence proteins in the immediate vicinity of PfSPM3, constituting its 'proxiome' and representing novel components of the SPMT network in developing gametocytes.\",\n      \"method\": \"Proximity-dependent biotinylation (BioID) followed by mass spectrometry\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID-MS identifies proximal proteins, single lab, but no reciprocal validation of individual interactions with SPM3 itself beyond spatial proximity\",\n      \"pmids\": [\"41358875\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"SPM3 (PF3D7_1327300) is a Plasmodium-specific subpellicular microtubule-associated protein that anchors subpellicular microtubules (SPMTs) to the inner membrane complex (IMC); its loss in P. falciparum disrupts SPMT organization and blocks falciform gametocyte morphogenesis, while its loss in P. berghei dissociates SPMTs from the IMC in sporozoites and severely impairs motility and salivary gland invasion, collectively establishing SPM3 as an essential structural linker between the SPMT cytoskeleton and the IMC across multiple Plasmodium life-cycle stages.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SPM3 (PF3D7_1327300) is a Plasmodium-specific microtubule-associated protein that functions as a structural linker anchoring subpellicular microtubules (SPMTs) to the inner membrane complex (IMC) across multiple life-cycle stages [#0, #1]. It is conserved within the genus Plasmodium (notably subgenus Laverania) but absent from other Apicomplexa [#0]. In P. falciparum, conditional knockdown and targeted disruption of SPM3 produce round, non-falciform gametocytes with an aberrant SPMT pattern, establishing a requirement for SPM3 in gametocyte morphogenesis [#0]. In P. berghei — which naturally has round gametocytes — SPM3 loss spares gametocytogenesis but causes aberrant sporozoite motility, a severe salivary gland invasion defect, and reduced transmission; electron microscopy shows increased separation between SPMTs and the IMC in knockout sporozoites, directly demonstrating that SPM3 tethers SPMTs to the IMC [#1]. Proximity-dependent biotinylation using SPM3 as bait in P. falciparum gametocytes has mapped a 37-protein proxiome representing candidate components of the SPMT network, but individual SPM3 interactions beyond spatial proximity have not been validated in the available corpus [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether a dedicated protein links the subpellicular microtubule cytoskeleton to gametocyte shape was unknown; genetic loss-of-function established SPM3 as required for falciform gametocyte morphogenesis in P. falciparum.\",\n      \"evidence\": \"Conditional knockdown and targeted gene disruption with live-cell and electron microscopy in P. falciparum\",\n      \"pmids\": [\"36625655\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not define the molecular mechanism by which SPM3 organizes the SPMT pattern\",\n        \"Direct binding partners at the IMC not identified in this study\",\n        \"Whether the morphological defect is a direct or downstream consequence of SPMT disorganization\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unclear whether SPM3's role was gametocyte-specific or reflected a general SPMT–IMC anchoring function; knockout in P. berghei showed SPM3 tethers SPMTs to the IMC and is required for sporozoite motility and mosquito transmission.\",\n      \"evidence\": \"Targeted gene knockout, electron microscopy showing increased SPMT–IMC distance, sporozoite motility assays, and mosquito transmission experiments in P. berghei\",\n      \"pmids\": [\"36625655\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular interface by which SPM3 bridges SPMTs and the IMC is not defined\",\n        \"Whether SPM3 binds microtubules directly or via intermediary proteins is unresolved\",\n        \"Species divergence: gametocyte morphogenesis phenotype seen in P. falciparum is absent in P. berghei, and the reason is not mechanistically explained\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The composition of the SPMT network around SPM3 was unknown; BioID mapping in gametocytes identified a proxiome of candidate SPMT-network components.\",\n      \"evidence\": \"Proximity-dependent biotinylation (BioID) with SPM3 as bait followed by mass spectrometry in P. falciparum gametocytes\",\n      \"pmids\": [\"41358875\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal validation of individual SPM3 interactions beyond spatial proximity\",\n        \"Direct binding partners versus mere neighborhood proteins not distinguished\",\n        \"Functional roles of the 37 identified proteins in SPMT anchoring not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular basis of SPM3-mediated SPMT–IMC anchoring — its microtubule-binding and IMC-binding interfaces and its direct partners — remains undetermined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of SPM3 or its binding domains\",\n        \"No validated direct interaction partner at the IMC or on microtubules\",\n        \"Mechanism of SPM3 recruitment and how it enforces SPMT spacing is unknown\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020039\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007017\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"SPM3 (PF3D7_1327300) anchors subpellicular microtubules to the inner membrane complex; loss increases SPMT–IMC distance in P. berghei sporozoites [#1].\",\n      \"Required for falciform gametocyte morphogenesis and normal SPMT patterning in P. falciparum [#0].\",\n      \"Required for sporozoite motility and salivary gland invasion, and thus mosquito transmission, in P. berghei [#1].\",\n      \"Conserved within genus Plasmodium (notably subgenus Laverania), absent in other Apicomplexa [#0].\",\n      \"BioID proxiome of 37 high-confidence proximal proteins in P. falciparum gametocytes represents candidate SPMT-network components; individual interactions with SPM3 not independently validated [#2].\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1327300","name":null,"product":"subpellicular microtubule protein 3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1342500","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1201300","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SPM3","evaluation":null}