{"gene":"PF3D7_0909500","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2023,"finding":"SPM1 (PF3D7_0909500) localizes to subpellicular microtubules (SPMTs) in P. falciparum gametocytes, as demonstrated by colocalization of overexpressed mCherry-tagged PfSPM1 with TubulinTracker and with PfSPM3-GFP; PfSPM1 showed a distribution similar to TubulinTracker along SPMTs with some cytosolic background, and its signal was distributed more basally compared to PfSPM3.","method":"Fluorescence microscopy colocalization of overexpressed mCherry-tagged PfSPM1 with TubulinTracker and GFP-tagged PfSPM3 in P. falciparum","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/colocalization approach, overexpressed tag, but two orthogonal colocalization partners used in one study","pmids":["36625655"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2023,"finding":"In P. falciparum sporozoites, cryo-electron tomography and subvolume averaging revealed that SPMTs are reinforced by an interrupted luminal helix (ILH) composed of TrxL1- and SPM1-like proteins. The ILH is present in the motile mosquito stages (ookinetes and sporozoites) but absent from merozoites and gametocytes. SPM1-GFP-expressing lines confirmed high expression in sporozoites.","method":"In situ cryo-electron tomography and subvolume averaging; SPM1-GFP live fluorescence imaging in sporozoites","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-ET structural determination with subvolume averaging plus GFP-tagging validation; structural finding replicated by fitting to existing Toxoplasma model","pmids":["36869034"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Single gene deletion of SPM1 in Plasmodium berghei showed it is dispensable for transmission from the vertebrate host to the mosquito and back, indicating SPM1 is not essential for transmission in the rodent malaria model.","method":"Single gene deletion (knockout) in P. berghei; mosquito transmission assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with defined transmission phenotype (negative result: dispensable), single lab","pmids":["39908102"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"Knockout of SPM1 in P. berghei (Δspm1) resulted in a statistically significant 57% reduction in salivary gland sporozoite counts compared to wild-type, suggesting a partial role in sporozoite infection of salivary glands, while the barcode sequencing screen found no strong transmission phenotype at the midgut stage.","method":"Conventional gene disruption vector; clonal knockout generation; sporozoite counts in salivary glands; barcode sequencing screen","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined quantitative phenotype (57% reduction in salivary gland sporozoites), single lab, single method","pmids":["37708854"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"c507"}]},{"year":2025,"finding":"SPM1 (PF3D7_0909500) was identified as a high-confidence component of the proxiome of PfSPM3 (a subpellicular MAP) in P. falciparum gametocytes by proximity-dependent biotinylation (BioID), confirming its association with the SPMT network. SPM1 was used as the significance threshold reference protein for defining high-confidence proxiome candidates.","method":"BioID proximity-dependent biotinylation with PfSPM3-BirA*-GFP as bait; streptavidin affinity purification; mass spectrometry; three independent biological replicates","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity biotinylation MS with three biological replicates, single lab, validates SPMT association of SPM1 as an established benchmark","pmids":["41358875"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"finding":"SPM1 is a transcriptional target of the AP2-O transcription factor in Plasmodium berghei ookinetes, as identified by chromatin immunoprecipitation-sequencing showing AP2-O binding to the upstream genomic region of the spm1 gene.","method":"Chromatin immunoprecipitation followed by sequencing (ChIP-seq)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — ChIP-seq is a direct binding assay, single lab, establishes transcriptional regulation of SPM1 by AP2-O in ookinetes","pmids":["26018192"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"SPM1 (PF3D7_0909500) is a subpellicular microtubule-associated protein that localizes to the SPMT lumen in P. falciparum, where it forms part of an interrupted luminal helix (together with TrxL1) specifically in motile mosquito stages (ookinetes and sporozoites) but not in merozoites or gametocytes; it is transcriptionally regulated by the AP2-O transcription factor in ookinetes, is a high-confidence component of the PfSPM3 proxiome in gametocytes, and while its deletion in P. berghei causes a partial reduction (~57%) in salivary gland sporozoite counts, it is largely dispensable for mosquito transmission."},"narrative":{"mechanistic_narrative":"SPM1 (PF3D7_0909500) is a subpellicular microtubule-associated protein of Plasmodium that contributes to the structural reinforcement of the subpellicular microtubule (SPMT) cytoskeleton [PMID:36625655, PMID:36869034]. In P. falciparum gametocytes, overexpressed PfSPM1 colocalizes with the microtubule marker TubulinTracker and with the SPMT protein PfSPM3 along the SPMTs, distributing more basally than PfSPM3 [PMID:36625655], and it is recovered as a high-confidence component of the PfSPM3 proxiome by proximity biotinylation, confirming its association with the SPMT network [PMID:41358875]. In situ cryo-electron tomography of P. falciparum sporozoites showed that SPMTs are reinforced by an interrupted luminal helix built from TrxL1- and SPM1-like proteins; this luminal structure is present in the motile mosquito stages (ookinetes and sporozoites) but absent from merozoites and gametocytes, and SPM1-GFP is highly expressed in sporozoites [PMID:36869034]. In the rodent parasite P. berghei, spm1 is a direct transcriptional target of the ookinete transcription factor AP2-O [PMID:26018192], and its deletion causes a partial (~57%) reduction in salivary gland sporozoite counts [PMID:37708854] but is otherwise dispensable for transmission through the mosquito [PMID:39908102]. Beyond its role as a luminal SPMT-reinforcing protein, the precise molecular contribution of SPM1 to microtubule mechanics has not been resolved in the available corpus.","teleology":[{"year":2015,"claim":"Establishing that spm1 is a defined transcriptional target of AP2-O placed SPM1 within the ookinete-stage gene expression program before its protein function was known.","evidence":"ChIP-seq mapping AP2-O binding to the spm1 upstream region in P. berghei ookinetes","pmids":["26018192"],"confidence":"Medium","gaps":["Does not demonstrate that AP2-O binding drives functional SPM1 expression","No protein-level or localization data from this study","Regulation in other stages or species not addressed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Colocalization of PfSPM1 with tubulin and PfSPM3 first assigned SPM1 to the subpellicular microtubule cytoskeleton, defining it as an SPMT-associated protein.","evidence":"Fluorescence colocalization of overexpressed mCherry-PfSPM1 with TubulinTracker and PfSPM3-GFP in P. falciparum gametocytes","pmids":["36625655"],"confidence":"Medium","gaps":["Relied on overexpressed tagged protein with cytosolic background","Does not resolve whether SPM1 binds microtubules directly or via other MAPs","Functional consequence of the SPMT localization untested"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2023,"claim":"Cryo-ET revealed the structural role of SPM1 as part of an interrupted luminal helix reinforcing SPMTs specifically in motile mosquito stages, explaining a stage-specific microtubule specialization.","evidence":"In situ cryo-electron tomography with subvolume averaging and SPM1-GFP imaging in P. falciparum sporozoites","pmids":["36869034"],"confidence":"High","gaps":["Exact stoichiometry and periodicity of SPM1 within the luminal helix not fully defined","Whether SPM1 loss abolishes the luminal helix not directly tested","Contribution of SPM1 versus TrxL1 to helix assembly unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Genetic disruption in P. berghei tested whether SPM1 is functionally required, showing a partial defect in salivary gland sporozoite colonization rather than an essential role.","evidence":"Clonal gene knockout and salivary gland sporozoite counts plus barcode sequencing screen in P. berghei","pmids":["37708854"],"confidence":"Medium","gaps":["Mechanism linking SPM1 loss to reduced salivary gland sporozoites unknown","Single lab, single method for the quantitative phenotype","Ultrastructural effect of knockout on SPMTs not examined"],"attribution":[{"species":"Plasmodium berghei","strain":"c507"}]},{"year":2025,"claim":"A dedicated transmission knockout confirmed that SPM1 is dispensable for the full mosquito-to-vertebrate transmission cycle, framing its role as modulatory rather than essential.","evidence":"Single gene deletion and mosquito transmission assays in P. berghei","pmids":["39908102"],"confidence":"Medium","gaps":["Does not exclude subtle motility or fitness defects","No P. falciparum knockout to confirm dispensability in the human parasite"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Proximity biotinylation independently validated the SPM1-SPMT network association by recovering SPM1 as a high-confidence PfSPM3 proxiome member in a physiologically tagged setting.","evidence":"BioID with PfSPM3-BirA*-GFP bait and mass spectrometry across three replicates in P. falciparum gametocytes","pmids":["41358875"],"confidence":"Medium","gaps":["Proximity does not establish direct SPM1-SPM3 binding","Single lab and single bait","Gametocyte context, while SPMT luminal helix is absent from gametocytes"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":null,"claim":"How SPM1 mechanically stabilizes or specializes the SPMT lumen and why its loss selectively impairs salivary gland invasion remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure-function dissection of the SPM1 microtubule-binding surface","No test of whether SPM1 deletion disrupts the interrupted luminal helix in vivo","Mechanistic basis for the salivary gland sporozoite defect unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Subpellicular microtubule interrupted luminal helix (with TrxL1-like proteins) [#1]"],"partners":["PFSPM3 (PROXIOME/COLOCALIZATION ASSOCIATION) [#0, #4]","TRXL1-LIKE PROTEIN (LUMINAL HELIX COMPONENT) [#1]","AP2-O (TRANSCRIPTIONAL REGULATOR OF SPM1) [#5]"],"other_free_text":["SPM1 (PF3D7_0909500) is a subpellicular microtubule protein; the interrupted luminal helix it forms is restricted to motile mosquito stages (ookinetes, sporozoites) and absent from merozoites and gametocytes [#1].","In P. berghei, spm1 deletion reduces salivary gland sporozoite counts by ~57% but is dispensable for transmission [#2, #3].","Corpus caution: much of the surrounding literature concerns partner/family proteins (PfSPM3, TrxL1); findings here are attributed specifically to SPM1/PF3D7_0909500."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"39908102","id":"PMC_39908102","title":"Microtubule inner proteins of Plasmodium are essential for transmission of malaria parasites.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/39908102","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41358875","id":"","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":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41531934","id":"","title":"Luminal acetylation of microtubules is not essential for Plasmodium berghei and Toxoplasma gondii survival.","date":"2025","source":"Microbial cell (Graz, Austria)","url":"https://pubmed.ncbi.nlm.nih.gov/41531934","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":false},{"pmid":"41626803","id":"","title":"Microtubule inner proteins in apicomplexan parasites.","date":"2026","source":"Biochemical Society transactions","url":"https://pubmed.ncbi.nlm.nih.gov/41626803","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36869034","id":"","title":"Variable microtubule architecture in the malaria parasite.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/36869034","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36625655","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37708854","id":"","title":"Identification of genes required for Plasmodium gametocyte-to-sporozoite development in the mosquito vector.","date":"2023","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/37708854","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"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":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35008492","id":"","title":"Systematic Analysis of Clemastine, a Candidate Apicomplexan Parasite-Selective Tubulin-Targeting Agent.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35008492","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31197225","id":"","title":"Antigenicity and immune correlate assessment of seven Plasmodium falciparum antigens in a longitudinal infant cohort from northern Ghana.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31197225","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39046777","id":"","title":"γ-tubulin complex controls the nucleation of tubulin-based structures in Apicomplexa.","date":"2024","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/39046777","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33665945","id":"","title":"Plasmodium transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes.","date":"2021","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/33665945","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33633135","id":"","title":"Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33633135","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26018192","id":"","title":"Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor.","date":"2015","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/26018192","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SPM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17403,"output_tokens":1801,"usd":0.039612,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6873,"output_tokens":2951,"usd":0.05407,"stage2_stop_reason":"end_turn"},"total_usd":0.093682,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"SPM1 (PF3D7_0909500) localizes to subpellicular microtubules (SPMTs) in P. falciparum gametocytes, as demonstrated by colocalization of overexpressed mCherry-tagged PfSPM1 with TubulinTracker and with PfSPM3-GFP; PfSPM1 showed a distribution similar to TubulinTracker along SPMTs with some cytosolic background, and its signal was distributed more basally compared to PfSPM3.\",\n      \"method\": \"Fluorescence microscopy colocalization of overexpressed mCherry-tagged PfSPM1 with TubulinTracker and GFP-tagged PfSPM3 in P. falciparum\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/colocalization approach, overexpressed tag, but two orthogonal colocalization partners used in one study\",\n      \"pmids\": [\"36625655\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In P. falciparum sporozoites, cryo-electron tomography and subvolume averaging revealed that SPMTs are reinforced by an interrupted luminal helix (ILH) composed of TrxL1- and SPM1-like proteins. The ILH is present in the motile mosquito stages (ookinetes and sporozoites) but absent from merozoites and gametocytes. SPM1-GFP-expressing lines confirmed high expression in sporozoites.\",\n      \"method\": \"In situ cryo-electron tomography and subvolume averaging; SPM1-GFP live fluorescence imaging in sporozoites\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-ET structural determination with subvolume averaging plus GFP-tagging validation; structural finding replicated by fitting to existing Toxoplasma model\",\n      \"pmids\": [\"36869034\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Single gene deletion of SPM1 in Plasmodium berghei showed it is dispensable for transmission from the vertebrate host to the mosquito and back, indicating SPM1 is not essential for transmission in the rodent malaria model.\",\n      \"method\": \"Single gene deletion (knockout) in P. berghei; mosquito transmission assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with defined transmission phenotype (negative result: dispensable), single lab\",\n      \"pmids\": [\"39908102\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Knockout of SPM1 in P. berghei (Δspm1) resulted in a statistically significant 57% reduction in salivary gland sporozoite counts compared to wild-type, suggesting a partial role in sporozoite infection of salivary glands, while the barcode sequencing screen found no strong transmission phenotype at the midgut stage.\",\n      \"method\": \"Conventional gene disruption vector; clonal knockout generation; sporozoite counts in salivary glands; barcode sequencing screen\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined quantitative phenotype (57% reduction in salivary gland sporozoites), single lab, single method\",\n      \"pmids\": [\"37708854\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"c507\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SPM1 (PF3D7_0909500) was identified as a high-confidence component of the proxiome of PfSPM3 (a subpellicular MAP) in P. falciparum gametocytes by proximity-dependent biotinylation (BioID), confirming its association with the SPMT network. SPM1 was used as the significance threshold reference protein for defining high-confidence proxiome candidates.\",\n      \"method\": \"BioID proximity-dependent biotinylation with PfSPM3-BirA*-GFP as bait; streptavidin affinity purification; mass spectrometry; three independent biological replicates\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity biotinylation MS with three biological replicates, single lab, validates SPMT association of SPM1 as an established benchmark\",\n      \"pmids\": [\"41358875\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"SPM1 is a transcriptional target of the AP2-O transcription factor in Plasmodium berghei ookinetes, as identified by chromatin immunoprecipitation-sequencing showing AP2-O binding to the upstream genomic region of the spm1 gene.\",\n      \"method\": \"Chromatin immunoprecipitation followed by sequencing (ChIP-seq)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — ChIP-seq is a direct binding assay, single lab, establishes transcriptional regulation of SPM1 by AP2-O in ookinetes\",\n      \"pmids\": [\"26018192\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"SPM1 (PF3D7_0909500) is a subpellicular microtubule-associated protein that localizes to the SPMT lumen in P. falciparum, where it forms part of an interrupted luminal helix (together with TrxL1) specifically in motile mosquito stages (ookinetes and sporozoites) but not in merozoites or gametocytes; it is transcriptionally regulated by the AP2-O transcription factor in ookinetes, is a high-confidence component of the PfSPM3 proxiome in gametocytes, and while its deletion in P. berghei causes a partial reduction (~57%) in salivary gland sporozoite counts, it is largely dispensable for mosquito transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SPM1 (PF3D7_0909500) is a subpellicular microtubule-associated protein of Plasmodium that contributes to the structural reinforcement of the subpellicular microtubule (SPMT) cytoskeleton [#0, #1]. In P. falciparum gametocytes, overexpressed PfSPM1 colocalizes with the microtubule marker TubulinTracker and with the SPMT protein PfSPM3 along the SPMTs, distributing more basally than PfSPM3 [#0], and it is recovered as a high-confidence component of the PfSPM3 proxiome by proximity biotinylation, confirming its association with the SPMT network [#4]. In situ cryo-electron tomography of P. falciparum sporozoites showed that SPMTs are reinforced by an interrupted luminal helix built from TrxL1- and SPM1-like proteins; this luminal structure is present in the motile mosquito stages (ookinetes and sporozoites) but absent from merozoites and gametocytes, and SPM1-GFP is highly expressed in sporozoites [#1]. In the rodent parasite P. berghei, spm1 is a direct transcriptional target of the ookinete transcription factor AP2-O [#5], and its deletion causes a partial (~57%) reduction in salivary gland sporozoite counts [#3] but is otherwise dispensable for transmission through the mosquito [#2]. Beyond its role as a luminal SPMT-reinforcing protein, the precise molecular contribution of SPM1 to microtubule mechanics has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Establishing that spm1 is a defined transcriptional target of AP2-O placed SPM1 within the ookinete-stage gene expression program before its protein function was known.\",\n      \"evidence\": \"ChIP-seq mapping AP2-O binding to the spm1 upstream region in P. berghei ookinetes\",\n      \"pmids\": [\"26018192\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not demonstrate that AP2-O binding drives functional SPM1 expression\",\n        \"No protein-level or localization data from this study\",\n        \"Regulation in other stages or species not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Colocalization of PfSPM1 with tubulin and PfSPM3 first assigned SPM1 to the subpellicular microtubule cytoskeleton, defining it as an SPMT-associated protein.\",\n      \"evidence\": \"Fluorescence colocalization of overexpressed mCherry-PfSPM1 with TubulinTracker and PfSPM3-GFP in P. falciparum gametocytes\",\n      \"pmids\": [\"36625655\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relied on overexpressed tagged protein with cytosolic background\",\n        \"Does not resolve whether SPM1 binds microtubules directly or via other MAPs\",\n        \"Functional consequence of the SPMT localization untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Cryo-ET revealed the structural role of SPM1 as part of an interrupted luminal helix reinforcing SPMTs specifically in motile mosquito stages, explaining a stage-specific microtubule specialization.\",\n      \"evidence\": \"In situ cryo-electron tomography with subvolume averaging and SPM1-GFP imaging in P. falciparum sporozoites\",\n      \"pmids\": [\"36869034\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Exact stoichiometry and periodicity of SPM1 within the luminal helix not fully defined\",\n        \"Whether SPM1 loss abolishes the luminal helix not directly tested\",\n        \"Contribution of SPM1 versus TrxL1 to helix assembly unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Genetic disruption in P. berghei tested whether SPM1 is functionally required, showing a partial defect in salivary gland sporozoite colonization rather than an essential role.\",\n      \"evidence\": \"Clonal gene knockout and salivary gland sporozoite counts plus barcode sequencing screen in P. berghei\",\n      \"pmids\": [\"37708854\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking SPM1 loss to reduced salivary gland sporozoites unknown\",\n        \"Single lab, single method for the quantitative phenotype\",\n        \"Ultrastructural effect of knockout on SPMTs not examined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"c507\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A dedicated transmission knockout confirmed that SPM1 is dispensable for the full mosquito-to-vertebrate transmission cycle, framing its role as modulatory rather than essential.\",\n      \"evidence\": \"Single gene deletion and mosquito transmission assays in P. berghei\",\n      \"pmids\": [\"39908102\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not exclude subtle motility or fitness defects\",\n        \"No P. falciparum knockout to confirm dispensability in the human parasite\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proximity biotinylation independently validated the SPM1-SPMT network association by recovering SPM1 as a high-confidence PfSPM3 proxiome member in a physiologically tagged setting.\",\n      \"evidence\": \"BioID with PfSPM3-BirA*-GFP bait and mass spectrometry across three replicates in P. falciparum gametocytes\",\n      \"pmids\": [\"41358875\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Proximity does not establish direct SPM1-SPM3 binding\",\n        \"Single lab and single bait\",\n        \"Gametocyte context, while SPMT luminal helix is absent from gametocytes\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SPM1 mechanically stabilizes or specializes the SPMT lumen and why its loss selectively impairs salivary gland invasion remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structure-function dissection of the SPM1 microtubule-binding surface\",\n        \"No test of whether SPM1 deletion disrupts the interrupted luminal helix in vivo\",\n        \"Mechanistic basis for the salivary gland sporozoite defect unknown\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Subpellicular microtubule interrupted luminal helix (with TrxL1-like proteins) [#1]\"],\n    \"partners\": [\"PfSPM3 (proxiome/colocalization association) [#0, #4]\", \"TrxL1-like protein (luminal helix component) [#1]\", \"AP2-O (transcriptional regulator of spm1) [#5]\"],\n    \"other_free_text\": [\n      \"SPM1 (PF3D7_0909500) is a subpellicular microtubule protein; the interrupted luminal helix it forms is restricted to motile mosquito stages (ookinetes, sporozoites) and absent from merozoites and gametocytes [#1].\",\n      \"In P. berghei, spm1 deletion reduces salivary gland sporozoite counts by ~57% but is dispensable for transmission [#2, #3].\",\n      \"Corpus caution: much of the surrounding literature concerns partner/family proteins (PfSPM3, TrxL1); findings here are attributed specifically to SPM1/PF3D7_0909500.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0909500","name":null,"product":"subpellicular microtubule protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0810700","name":null,"product":"subpellicular microtubule protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0707500","name":null,"product":"subpellicular microtubule protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SPM1","evaluation":null}