{"gene":"PF3D7_0616500","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2008,"finding":"TLP (PF3D7_0616500) is a member of the TRAP/MIC2 family expressed predominantly in salivary gland sporozoites of P. falciparum and P. berghei. Targeted disruption of P. berghei TLP resulted in decreased capacity for cell traversal by sporozoites and reduced infectivity in vivo, whereas in vitro sporozoite motility and hepatocyte invasion were unaffected, indicating a specific role in cell traversal.","method":"Targeted gene disruption (knockout), quantitative RT-PCR for expression analysis, cell traversal assay, in vivo infectivity assay","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with specific phenotypic readout (cell traversal defect) and negative controls (motility and invasion unaffected), single lab but multiple orthogonal assays","pmids":["18346224"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"TLP (PF3D7_0616500) binds aldolase via its cytoplasmic tail, establishing it as a functional member of the TRAP family that links extracellular adhesion to the parasite actin-myosin motor. Targeted gene disruption of TLP in P. berghei revealed a nonvital, redundant role during life cycle progression.","method":"Aldolase-binding assay (in vitro), genetic complementation test, targeted gene disruption","journal":"Eukaryotic cell","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro aldolase binding assay combined with genetic disruption and complementation, single lab with multiple orthogonal methods","pmids":["18441124"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"finding":"TLP (PF3D7_0616500) plays a specific role in sporozoite adhesion under static conditions; tlp(-) sporozoites move 4 times less efficiently than wild-type sporozoites in vitro, and TLP acts in concert with TRAP and S6 and with actin filaments to organize efficient sporozoite adhesion prior to initiating motility and host cell invasion.","method":"Total internal reflection fluorescence (TIRF) microscopy, flow adhesion assay, analysis of tlp(-) knockout sporozoites","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct imaging of tlp(-) mutant sporozoites with quantitative motility readout, single lab","pmids":["20159960"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"finding":"TLP (PF3D7_0616500) surface adhesin function is required for normal sporozoite migration in structured environments; tlp(-) sporozoites show adhesion impairment that disrupts the correlation between speed, persistence length and dispersal, explaining their delay in infecting the host. TLP-lacking sporozoites show impaired intradermal movement.","method":"In vivo intravital imaging, micro-fabricated obstacle array assays, analysis of tlp(-) knockout sporozoites","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative motility analysis in vivo and in vitro using tlp(-) mutants, single lab","pmids":["21698220"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"finding":"TLP (PF3D7_0616500) knockout sporozoites (tlp ko) are defective in cell traversal and are retained inside the MDCK cytoplasm rather than passing through, providing direct evidence that TLP is required for productive cell traversal (passage through) rather than merely cell wounding.","method":"MDCK monolayer cell traversal assay with TLP-knockout sporozoites, fluorescence microscopy","journal":"Journal of immunological methods","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional assay with genetic knockout and microscopic confirmation of retention phenotype, single lab","pmids":["22306356"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"TLP (PF3D7_0616500) functions in reducing retrograde flow for the buildup of adhesive force during malaria parasite gliding motility; tlp(-) sporozoites show higher retrograde flow rates but lower force generation, indicating TLP modulates actin dynamics or actin filament organization to couple retrograde flow to forward force production.","method":"Optical tweezers measurements of retrograde flow and force in tlp(-) versus wild-type sporozoites","journal":"ACS nano","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biophysical measurement using optical tweezers on tlp(-) knockout sporozoites, single lab, novel mechanistic readout","pmids":["26792112"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"TLP (PF3D7_0616500) is secreted from micronemes to the sporozoite surface via a PAT (putative pantothenate transporter)-dependent exocytosis mechanism; P. berghei sporozoites lacking PAT fail to secrete TRAP-family adhesins including those in micronemes and are immotile, placing TLP secretion downstream of PAT-regulated vesicle fusion.","method":"Genetic disruption of PAT, secretion assays, motility assays in P. berghei","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — PAT knockout affects a broad class of microneme-resident proteins; TLP is implicated indirectly as part of the TRAP-family secretory vesicle class, not individually confirmed","pmids":["27427910"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"TLP (PF3D7_0616500) is an important element of the force-generating machinery during sporozoite gliding motility; tlp(-) sporozoites show lower traction forces on the ventral (substrate-facing) surface with distinct but reduced force foci compared to wild-type sporozoites, as measured by traction force microscopy.","method":"Traction force microscopy on wild-type and tlp(-) sporozoites","journal":"Journal of microscopy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biophysical measurement (traction force microscopy) on tlp(-) knockout sporozoites with quantitative force readout, single lab","pmids":["40716091"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"TLP (PF3D7_0616500) is a TRAP/MIC2-family type I transmembrane protein expressed in Plasmodium sporozoites whose cytoplasmic tail binds aldolase to link the extracellular domain to the actin-myosin motor; it is specifically required for cell traversal and intradermal migration, functions in organizing sporozoite adhesion and modulating actin dynamics to couple retrograde flow to traction force generation, but is dispensable for in vitro gliding motility and hepatocyte invasion per se, consistent with a redundant yet non-vital invasin role."},"narrative":{"mechanistic_narrative":"TLP (PF3D7_0616500) is a TRAP/MIC2-family type I transmembrane adhesin expressed predominantly in salivary-gland sporozoites of P. falciparum and P. berghei that is specifically required for productive cell traversal and efficient intradermal migration [PMID:18346224, PMID:22306356]. As a functional TRAP-family member, its cytoplasmic tail binds aldolase, physically coupling extracellular adhesion to the parasite actin-myosin motor, yet genetic disruption in P. berghei shows the protein is non-vital and redundant during life-cycle progression, leaving in vitro gliding motility and hepatocyte invasion per se intact [PMID:18346224, PMID:18441124]. Beyond invasin function, TLP organizes sporozoite adhesion, acting together with TRAP, S6, and actin filaments to establish efficient attachment before motility, such that tlp(-) sporozoites adhere and disperse abnormally and are delayed in infecting the host [PMID:20159960, PMID:21698220]. Biophysically, TLP modulates actin dynamics to couple retrograde actin flow to traction-force generation: tlp(-) sporozoites exhibit elevated retrograde flow but reduced force output and lower, disorganized ventral traction forces, marking TLP as an element of the sporozoite force-generating machinery [PMID:26792112, PMID:40716091]. All mechanistic characterization derives from P. berghei knockout studies; no direct biochemical or structural analysis of the P. falciparum protein appears in the available corpus.","teleology":[{"year":2008,"claim":"Establishing whether TLP had a distinct role among TRAP-family adhesins, targeted disruption defined it as specifically required for sporozoite cell traversal rather than motility or invasion.","evidence":"targeted gene knockout in P. berghei with cell traversal, in vitro motility, and in vivo infectivity assays","pmids":["18346224"],"confidence":"High","gaps":["Molecular basis of the traversal-specific requirement not defined","No characterization of the P. falciparum protein directly","Extracellular ligand/receptor not identified"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"claim":"To connect TLP's surface adhesion to the motor, aldolase binding by its cytoplasmic tail was shown, placing TLP in the TRAP-family adhesion-to-actomyosin linkage while genetics confirmed a redundant, non-vital role.","evidence":"in vitro aldolase-binding assay with genetic disruption and complementation in P. berghei","pmids":["18441124"],"confidence":"High","gaps":["Direct structural definition of the tail-aldolase interface absent","Extent of functional redundancy with other TRAP-family members unquantified"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"claim":"Asking how TLP contributes before motility begins, imaging showed it organizes efficient sporozoite adhesion under static conditions in concert with TRAP, S6, and actin filaments.","evidence":"TIRF microscopy and flow adhesion assays on tlp(-) versus wild-type P. berghei sporozoites","pmids":["20159960"],"confidence":"Medium","gaps":["Direct physical interaction between TLP, TRAP, and S6 not demonstrated","Mechanism of adhesion organization unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"claim":"To explain infection delay in vivo, quantitative migration analysis linked TLP-dependent adhesion to normal coupling of speed, persistence, and dispersal in structured environments.","evidence":"intravital imaging and micro-fabricated obstacle arrays with tlp(-) P. berghei sporozoites","pmids":["21698220"],"confidence":"Medium","gaps":["Molecular determinants of adhesion strength not mapped","Contribution of specific tissue substrates unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"claim":"Distinguishing wounding from passage, knockout sporozoites were shown to be retained inside host cytoplasm, establishing TLP as required for productive traversal (passage-through) rather than mere cell wounding.","evidence":"MDCK monolayer traversal assay with fluorescence microscopy of tlp knockout P. berghei sporozoites","pmids":["22306356"],"confidence":"Medium","gaps":["Egress step defect not mechanistically defined","Molecular partners at the exit membrane unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Probing how TLP shapes force production, optical tweezers revealed that tlp(-) sporozoites have higher retrograde flow but lower force, implicating TLP in coupling actin retrograde flow to adhesive force buildup.","evidence":"optical tweezers measurement of retrograde flow and force in tlp(-) versus wild-type P. berghei sporozoites","pmids":["26792112"],"confidence":"Medium","gaps":["Direct effect of TLP on actin filament dynamics not visualized","Whether TLP acts through aldolase-actin linkage in this context untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"Addressing how TLP reaches the surface, a PAT knockout that blocks secretion of TRAP-family microneme adhesins implicated TLP secretion downstream of PAT-regulated vesicle fusion.","evidence":"PAT genetic disruption with secretion and motility assays in P. berghei","pmids":["27427910"],"confidence":"Low","gaps":["TLP secretion inferred as part of a broad TRAP-family class, not individually confirmed","Direct demonstration of TLP micronemal residence and PAT-dependent surface delivery absent"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Directly measuring traction, force microscopy showed tlp(-) sporozoites generate lower and disorganized ventral traction forces, confirming TLP as an element of the sporozoite force-generating machinery.","evidence":"traction force microscopy on wild-type and tlp(-) P. berghei sporozoites","pmids":["40716091"],"confidence":"Medium","gaps":["Molecular link between TLP and traction foci organization unresolved","Relationship to the aldolase-actin motor connection not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How TLP molecularly organizes adhesion and actin dynamics to enable traversal, and whether the P. falciparum protein behaves as its P. berghei ortholog, remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No extracellular ligand/receptor identified","No structural model of the adhesin or its aldolase-binding tail","P. falciparum TLP not functionally characterized directly"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ALDOLASE","TRAP","S6","ACTIN FILAMENTS"],"other_free_text":["TRAP/MIC2-family type I transmembrane adhesin expressed predominantly in salivary-gland sporozoites [#0].","Cytoplasmic tail binds aldolase, linking extracellular adhesion to the actin-myosin motor [#1].","Specifically required for productive cell traversal (passage-through, not wounding) and intradermal migration; dispensable for in vitro gliding and hepatocyte invasion [#0, #4].","Modulates actin retrograde flow and traction-force generation during gliding [#5, #7].","Non-vital, redundant role in P. berghei life-cycle progression [#1].","All functional data derive from P. berghei knockouts; P. falciparum protein not directly characterized in the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"9267031","id":"PMC_9267031","title":"TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites.","date":"1997","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/9267031","citation_count":508,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TRAP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28422178","id":"PMC_28422178","title":"Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine.","date":"2017","source":"Scientific 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Targeted disruption of P. berghei TLP resulted in decreased capacity for cell traversal by sporozoites and reduced infectivity in vivo, whereas in vitro sporozoite motility and hepatocyte invasion were unaffected, indicating a specific role in cell traversal.\",\n      \"method\": \"Targeted gene disruption (knockout), quantitative RT-PCR for expression analysis, cell traversal assay, in vivo infectivity assay\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with specific phenotypic readout (cell traversal defect) and negative controls (motility and invasion unaffected), single lab but multiple orthogonal assays\",\n      \"pmids\": [\"18346224\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"TLP (PF3D7_0616500) binds aldolase via its cytoplasmic tail, establishing it as a functional member of the TRAP family that links extracellular adhesion to the parasite actin-myosin motor. Targeted gene disruption of TLP in P. berghei revealed a nonvital, redundant role during life cycle progression.\",\n      \"method\": \"Aldolase-binding assay (in vitro), genetic complementation test, targeted gene disruption\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro aldolase binding assay combined with genetic disruption and complementation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"18441124\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"TLP (PF3D7_0616500) plays a specific role in sporozoite adhesion under static conditions; tlp(-) sporozoites move 4 times less efficiently than wild-type sporozoites in vitro, and TLP acts in concert with TRAP and S6 and with actin filaments to organize efficient sporozoite adhesion prior to initiating motility and host cell invasion.\",\n      \"method\": \"Total internal reflection fluorescence (TIRF) microscopy, flow adhesion assay, analysis of tlp(-) knockout sporozoites\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct imaging of tlp(-) mutant sporozoites with quantitative motility readout, single lab\",\n      \"pmids\": [\"20159960\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"TLP (PF3D7_0616500) surface adhesin function is required for normal sporozoite migration in structured environments; tlp(-) sporozoites show adhesion impairment that disrupts the correlation between speed, persistence length and dispersal, explaining their delay in infecting the host. TLP-lacking sporozoites show impaired intradermal movement.\",\n      \"method\": \"In vivo intravital imaging, micro-fabricated obstacle array assays, analysis of tlp(-) knockout sporozoites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative motility analysis in vivo and in vitro using tlp(-) mutants, single lab\",\n      \"pmids\": [\"21698220\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"TLP (PF3D7_0616500) knockout sporozoites (tlp ko) are defective in cell traversal and are retained inside the MDCK cytoplasm rather than passing through, providing direct evidence that TLP is required for productive cell traversal (passage through) rather than merely cell wounding.\",\n      \"method\": \"MDCK monolayer cell traversal assay with TLP-knockout sporozoites, fluorescence microscopy\",\n      \"journal\": \"Journal of immunological methods\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional assay with genetic knockout and microscopic confirmation of retention phenotype, single lab\",\n      \"pmids\": [\"22306356\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TLP (PF3D7_0616500) functions in reducing retrograde flow for the buildup of adhesive force during malaria parasite gliding motility; tlp(-) sporozoites show higher retrograde flow rates but lower force generation, indicating TLP modulates actin dynamics or actin filament organization to couple retrograde flow to forward force production.\",\n      \"method\": \"Optical tweezers measurements of retrograde flow and force in tlp(-) versus wild-type sporozoites\",\n      \"journal\": \"ACS nano\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biophysical measurement using optical tweezers on tlp(-) knockout sporozoites, single lab, novel mechanistic readout\",\n      \"pmids\": [\"26792112\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TLP (PF3D7_0616500) is secreted from micronemes to the sporozoite surface via a PAT (putative pantothenate transporter)-dependent exocytosis mechanism; P. berghei sporozoites lacking PAT fail to secrete TRAP-family adhesins including those in micronemes and are immotile, placing TLP secretion downstream of PAT-regulated vesicle fusion.\",\n      \"method\": \"Genetic disruption of PAT, secretion assays, motility assays in P. berghei\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — PAT knockout affects a broad class of microneme-resident proteins; TLP is implicated indirectly as part of the TRAP-family secretory vesicle class, not individually confirmed\",\n      \"pmids\": [\"27427910\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TLP (PF3D7_0616500) is an important element of the force-generating machinery during sporozoite gliding motility; tlp(-) sporozoites show lower traction forces on the ventral (substrate-facing) surface with distinct but reduced force foci compared to wild-type sporozoites, as measured by traction force microscopy.\",\n      \"method\": \"Traction force microscopy on wild-type and tlp(-) sporozoites\",\n      \"journal\": \"Journal of microscopy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biophysical measurement (traction force microscopy) on tlp(-) knockout sporozoites with quantitative force readout, single lab\",\n      \"pmids\": [\"40716091\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TLP (PF3D7_0616500) is a TRAP/MIC2-family type I transmembrane protein expressed in Plasmodium sporozoites whose cytoplasmic tail binds aldolase to link the extracellular domain to the actin-myosin motor; it is specifically required for cell traversal and intradermal migration, functions in organizing sporozoite adhesion and modulating actin dynamics to couple retrograde flow to traction force generation, but is dispensable for in vitro gliding motility and hepatocyte invasion per se, consistent with a redundant yet non-vital invasin role.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TLP (PF3D7_0616500) is a TRAP/MIC2-family type I transmembrane adhesin expressed predominantly in salivary-gland sporozoites of P. falciparum and P. berghei that is specifically required for productive cell traversal and efficient intradermal migration [#0, #4]. As a functional TRAP-family member, its cytoplasmic tail binds aldolase, physically coupling extracellular adhesion to the parasite actin-myosin motor, yet genetic disruption in P. berghei shows the protein is non-vital and redundant during life-cycle progression, leaving in vitro gliding motility and hepatocyte invasion per se intact [#0, #1]. Beyond invasin function, TLP organizes sporozoite adhesion, acting together with TRAP, S6, and actin filaments to establish efficient attachment before motility, such that tlp(-) sporozoites adhere and disperse abnormally and are delayed in infecting the host [#2, #3]. Biophysically, TLP modulates actin dynamics to couple retrograde actin flow to traction-force generation: tlp(-) sporozoites exhibit elevated retrograde flow but reduced force output and lower, disorganized ventral traction forces, marking TLP as an element of the sporozoite force-generating machinery [#5, #7]. All mechanistic characterization derives from P. berghei knockout studies; no direct biochemical or structural analysis of the P. falciparum protein appears in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Establishing whether TLP had a distinct role among TRAP-family adhesins, targeted disruption defined it as specifically required for sporozoite cell traversal rather than motility or invasion.\",\n      \"evidence\": \"targeted gene knockout in P. berghei with cell traversal, in vitro motility, and in vivo infectivity assays\",\n      \"pmids\": [\"18346224\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of the traversal-specific requirement not defined\", \"No characterization of the P. falciparum protein directly\", \"Extracellular ligand/receptor not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"To connect TLP's surface adhesion to the motor, aldolase binding by its cytoplasmic tail was shown, placing TLP in the TRAP-family adhesion-to-actomyosin linkage while genetics confirmed a redundant, non-vital role.\",\n      \"evidence\": \"in vitro aldolase-binding assay with genetic disruption and complementation in P. berghei\",\n      \"pmids\": [\"18441124\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct structural definition of the tail-aldolase interface absent\", \"Extent of functional redundancy with other TRAP-family members unquantified\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Asking how TLP contributes before motility begins, imaging showed it organizes efficient sporozoite adhesion under static conditions in concert with TRAP, S6, and actin filaments.\",\n      \"evidence\": \"TIRF microscopy and flow adhesion assays on tlp(-) versus wild-type P. berghei sporozoites\",\n      \"pmids\": [\"20159960\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical interaction between TLP, TRAP, and S6 not demonstrated\", \"Mechanism of adhesion organization unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"To explain infection delay in vivo, quantitative migration analysis linked TLP-dependent adhesion to normal coupling of speed, persistence, and dispersal in structured environments.\",\n      \"evidence\": \"intravital imaging and micro-fabricated obstacle arrays with tlp(-) P. berghei sporozoites\",\n      \"pmids\": [\"21698220\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular determinants of adhesion strength not mapped\", \"Contribution of specific tissue substrates unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Distinguishing wounding from passage, knockout sporozoites were shown to be retained inside host cytoplasm, establishing TLP as required for productive traversal (passage-through) rather than mere cell wounding.\",\n      \"evidence\": \"MDCK monolayer traversal assay with fluorescence microscopy of tlp knockout P. berghei sporozoites\",\n      \"pmids\": [\"22306356\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Egress step defect not mechanistically defined\", \"Molecular partners at the exit membrane unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Probing how TLP shapes force production, optical tweezers revealed that tlp(-) sporozoites have higher retrograde flow but lower force, implicating TLP in coupling actin retrograde flow to adhesive force buildup.\",\n      \"evidence\": \"optical tweezers measurement of retrograde flow and force in tlp(-) versus wild-type P. berghei sporozoites\",\n      \"pmids\": [\"26792112\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct effect of TLP on actin filament dynamics not visualized\", \"Whether TLP acts through aldolase-actin linkage in this context untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Addressing how TLP reaches the surface, a PAT knockout that blocks secretion of TRAP-family microneme adhesins implicated TLP secretion downstream of PAT-regulated vesicle fusion.\",\n      \"evidence\": \"PAT genetic disruption with secretion and motility assays in P. berghei\",\n      \"pmids\": [\"27427910\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"TLP secretion inferred as part of a broad TRAP-family class, not individually confirmed\", \"Direct demonstration of TLP micronemal residence and PAT-dependent surface delivery absent\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Directly measuring traction, force microscopy showed tlp(-) sporozoites generate lower and disorganized ventral traction forces, confirming TLP as an element of the sporozoite force-generating machinery.\",\n      \"evidence\": \"traction force microscopy on wild-type and tlp(-) P. berghei sporozoites\",\n      \"pmids\": [\"40716091\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular link between TLP and traction foci organization unresolved\", \"Relationship to the aldolase-actin motor connection not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TLP molecularly organizes adhesion and actin dynamics to enable traversal, and whether the P. falciparum protein behaves as its P. berghei ortholog, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No extracellular ligand/receptor identified\", \"No structural model of the adhesin or its aldolase-binding tail\", \"P. falciparum TLP not functionally characterized directly\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0050839\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0051015\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009986\", \"supporting_discovery_ids\": [2, 3, 6]},\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035891\", \"supporting_discovery_ids\": [2, 3, 5, 7]},\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"aldolase\", \"TRAP\", \"S6\", \"actin filaments\"],\n    \"other_free_text\": [\n      \"TRAP/MIC2-family type I transmembrane adhesin expressed predominantly in salivary-gland sporozoites [#0].\",\n      \"Cytoplasmic tail binds aldolase, linking extracellular adhesion to the actin-myosin motor [#1].\",\n      \"Specifically required for productive cell traversal (passage-through, not wounding) and intradermal migration; dispensable for in vitro gliding and hepatocyte invasion [#0, #4].\",\n      \"Modulates actin retrograde flow and traction-force generation during gliding [#5, #7].\",\n      \"Non-vital, redundant role in P. berghei life-cycle progression [#1].\",\n      \"All functional data derive from P. berghei knockouts; P. falciparum protein not directly characterized in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0616500","name":null,"product":"TRAP-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1116000","name":null,"product":"TRAP-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1133500","name":null,"product":"TRAP-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"TLP","evaluation":null}