{"gene":"PF3D7_0616200","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2020,"finding":"NDC80 in Plasmodium berghei localizes to kinetochores and displays dynamic spatiotemporal changes during proliferation, including highly unusual kinetochore arrangements during sexual stages. A very divergent candidate for the SPC24 subunit was identified, completing a canonical NDC80 complex structure in Plasmodium. Live-cell imaging revealed NDC80 as part of the outer kinetochore complex that attaches centromeres to spindle microtubules during atypical endomitosis and endoreduplication.","method":"NDC80-GFP live-cell imaging in P. berghei, proteomics/complex composition analysis, identification of divergent SPC24 subunit","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live-cell imaging with functional localization data and complex composition identification in a single lab using multiple methods","pmids":["32501284"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"finding":"NDC80 fluorescence (together with ChIP-seq) was used to identify SMC2/SMC4 condensin subunit localization to centromeres during early schizogony in P. berghei, confirming NDC80 as a centromere/kinetochore marker at this stage. This establishes NDC80's spatial position at centromeres during endomitotic schizogony.","method":"Co-localization of NDC80-GFP with SMC2/SMC4 fluorescent fusions; ChIP-seq to confirm centromeric localization","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — NDC80 used as validated kinetochore/centromere marker with orthogonal ChIP-seq confirmation, single lab","pmids":["32049018"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"In P. falciparum gametocytes, NDC80 (PfNDC80) participates in a non-mitotic hemispindle associated with nuclear microtubule assembly/disassembly at a non-mitotic MTOC embedded in the nuclear membrane, driving nuclear elongation, chromatin reorganization, IMC positioning, and subpellicular microtubule formation. Depolymerization of microtubules with trifluralin disrupted NDC80-associated kinetochore organization, linking NDC80 function to the non-mitotic microtubule machinery in gametocytes.","method":"3D electron microscopy, fluorescence imaging of PfNDC80 in gametocytes, microtubule depolymerization with trifluralin","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by fluorescence with functional perturbation (trifluralin), orthogonal 3D EM, single lab","pmids":["36030238"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"SAS4, a basal body component in Plasmodium, does NOT associate with NDC80, establishing that NDC80 is specifically part of the nuclear envelope/centriolar plaque MTOC and not part of the cytoplasmic basal body/outer centriolar MTOC in male gametocytes.","method":"Co-localization and co-immunoprecipitation/fluorescence assays comparing SAS4 and NDC80 localization in P. berghei male gametocytes","journal":"Life science alliance","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single negative co-localization result used to delineate NDC80's organelle specificity, single lab, single method","pmids":["35550346"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"Conditional disruption of PfNDC80 (along with PfNuf2) in P. falciparum causes aberrant mitotic spindle organisation, loss of CENH3 centromere marker integrity, impaired karyokinesis, and—unexpectedly—disengagement of the centriolar plaque (centrosome equivalent) from the nuclear envelope. This leads to formation of anucleate merozoites, revealing that correct kinetochore/spindle complex assembly is required both for chromosome segregation and for positioning the nascent apical complex.","method":"Conditional disruption of PfNDC80, ultrastructure-expansion microscopy, fluorescence imaging of spindle/centromere/apical complex markers","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional genetic disruption with defined cellular phenotypes confirmed by ultrastructure-expansion microscopy and multiple fluorescent markers, peer-reviewed","pmids":["38987258"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Kinesin-5 partially co-localizes with NDC80 during early blood stage schizogony and is closely associated with NDC80 during male gametogony in P. berghei, establishing that NDC80 marks kinetochore/spindle regions with which kinesin-5 associates during nuclear division.","method":"Fixed-cell immunofluorescence co-localization of kinesin-5 with NDC80, dual-color live-cell imaging in P. berghei","journal":"Frontiers in cellular and infection microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-localization only (no biochemical interaction confirmed), single lab, single method for the NDC80-specific finding","pmids":["33154955"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_0616200 (NDC80) is a kinetochore component that forms part of the canonical outer kinetochore NDC80 complex (including a divergent SPC24 subunit) in Plasmodium, localizing dynamically to centromeres/kinetochores at the nuclear envelope MTOC during atypical endomitosis and endoreduplication; conditional disruption of PfNDC80 in P. falciparum disrupts spindle organization, centromere integrity, and centriolar plaque attachment to the nuclear envelope, causing failed karyokinesis and anucleate merozoites, while in gametocytes NDC80 participates in a non-mitotic hemispindle that drives nuclear elongation and chromatin reorganization."},"narrative":{"mechanistic_narrative":"PF3D7_0616200 (NDC80) is an outer-kinetochore component that couples centromeres to spindle microtubules during the atypical, closed nuclear divisions of Plasmodium [PMID:32501284, PMID:38987258]. In P. berghei, NDC80 localizes to kinetochores with dynamic spatiotemporal behavior across proliferative and sexual stages and assembles into a canonical NDC80 complex that includes a highly divergent SPC24 subunit [PMID:32501284]; it serves as a validated centromere/kinetochore marker, co-positioning with centromeric condensin (SMC2/SMC4) during early schizogony [PMID:32049018]. NDC80 is a component specifically of the nuclear-envelope-embedded centriolar plaque MTOC rather than the cytoplasmic basal body, as it does not associate with the basal body component SAS4 [PMID:35550346]. Conditional disruption of PfNDC80 in P. falciparum causes aberrant mitotic spindle organization, loss of CENH3 centromere integrity, and failed karyokinesis, and unexpectedly detaches the centriolar plaque from the nuclear envelope, yielding anucleate merozoites — establishing that correct NDC80/spindle assembly is required both for chromosome segregation and for positioning the nascent apical complex [PMID:38987258]. Beyond mitosis, in P. falciparum gametocytes NDC80 participates in a non-mitotic hemispindle at a nuclear-membrane MTOC that drives nuclear elongation and chromatin reorganization, and its kinetochore organization depends on intact microtubules [PMID:36030238].","teleology":[{"year":2020,"claim":"Establishing whether Plasmodium builds a canonical outer kinetochore, this work placed NDC80 at kinetochores throughout proliferation and identified a divergent SPC24 that completes an NDC80 complex, defining the molecular machinery linking centromeres to spindle microtubules in atypical division.","evidence":"NDC80-GFP live-cell imaging and complex-composition proteomics in P. berghei","pmids":["32501284"],"confidence":"Medium","gaps":["Direct microtubule-binding activity of the NDC80 complex not biochemically reconstituted","Stoichiometry and full subunit composition of the divergent complex not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"claim":"By using NDC80 as a validated kinetochore/centromere marker co-localizing with condensin subunits, the study fixed NDC80's spatial position at centromeres during endomitotic schizogony.","evidence":"Co-localization of NDC80-GFP with SMC2/SMC4 fusions plus ChIP-seq confirmation in P. berghei","pmids":["32049018"],"confidence":"Medium","gaps":["Does not test whether NDC80 recruits or depends on condensin","NDC80 role here is inferred as a marker, not directly perturbed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"claim":"To connect kinetochores to spindle motor activity, kinesin-5 was shown to associate with NDC80-marked regions during schizogony and gametogony, positioning NDC80 near the spindle motor machinery.","evidence":"Fixed-cell and dual-color live imaging of kinesin-5 with NDC80 in P. berghei","pmids":["33154955"],"confidence":"Low","gaps":["Co-localization only; no biochemical or direct interaction demonstrated","Functional dependence between NDC80 and kinesin-5 untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"Distinguishing which MTOC NDC80 belongs to, the absence of association with the basal body protein SAS4 assigned NDC80 specifically to the nuclear-envelope centriolar plaque MTOC rather than the cytoplasmic basal body in male gametocytes.","evidence":"Comparative co-localization and co-IP of SAS4 vs NDC80 in P. berghei male gametocytes","pmids":["35550346"],"confidence":"Low","gaps":["Rests on a single negative result, not independently confirmed","Does not define what tethers NDC80 to the centriolar plaque MTOC"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"Extending NDC80 beyond mitosis, this work showed NDC80 functions in a non-mitotic hemispindle during gametocyte development, linking it to microtubule-dependent nuclear elongation and chromatin reorganization.","evidence":"3D electron microscopy, PfNDC80 fluorescence imaging, and trifluralin microtubule depolymerization in P. falciparum gametocytes","pmids":["36030238"],"confidence":"Medium","gaps":["Mechanism by which NDC80 organizes non-mitotic microtubules undefined","Whether the gametocyte NDC80 complex differs in composition from the mitotic one unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Answering what NDC80 is functionally required for, conditional disruption revealed that loss of PfNDC80 disrupts spindle and centromere integrity, blocks karyokinesis, and detaches the centriolar plaque from the nuclear envelope, coupling kinetochore assembly to both chromosome segregation and apical-complex positioning.","evidence":"Conditional disruption of PfNDC80 with ultrastructure-expansion microscopy and spindle/centromere/apical marker imaging in P. falciparum","pmids":["38987258"],"confidence":"High","gaps":["Molecular basis of centriolar-plaque tethering to the nuclear envelope not identified","Direct versus indirect contribution of NDC80 to apical complex positioning unresolved","Effect co-attributed with PfNuf2; NDC80-specific separable role not isolated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How the divergent Plasmodium NDC80 complex physically binds spindle microtubules and how it is recruited to and tethered at the nuclear-envelope centriolar plaque remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted microtubule-binding assay for the Plasmodium NDC80 complex","Recruitment/tethering mechanism to the centriolar plaque MTOC unknown","Structural model of the divergent complex lacking"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["NDC80 complex (with divergent SPC24 subunit)"],"partners":["SPC24 (DIVERGENT SUBUNIT)","PFNUF2","KINESIN-5 (CO-LOCALIZATION)","SMC2/SMC4 CONDENSIN (CENTROMERIC CO-LOCALIZATION)"],"other_free_text":["Marks the nuclear-envelope centriolar plaque MTOC and is excluded from the cytoplasmic SAS4-associated basal body MTOC","Functions in a non-mitotic hemispindle during P. falciparum gametocyte nuclear elongation","Disruption detaches the centriolar plaque from the nuclear envelope, producing anucleate merozoites"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32501284","id":"PMC_32501284","title":"Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/32501284","citation_count":47,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NDC80"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36030238","id":"PMC_36030238","title":"Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/36030238","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNDC80"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32049018","id":"PMC_32049018","title":"Plasmodium Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission.","date":"2020","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/32049018","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NDC80"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35550346","id":"PMC_35550346","title":"Plasmodium SAS4: basal body component of male cell which is dispensable for parasite transmission.","date":"2022","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/35550346","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NDC80","kinetochore protein NDC80"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38987258","id":"PMC_38987258","title":"Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38987258","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNDC80"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33154955","id":"PMC_33154955","title":"Plasmodium berghei Kinesin-5 Associates With the Spindle Apparatus During Cell Division and Is Important for Efficient Production of Infectious Sporozoites.","date":"2020","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33154955","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NDC80"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5533,"output_tokens":1878,"usd":0.022385,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7015,"output_tokens":3146,"usd":0.056863,"stage2_stop_reason":"end_turn"},"total_usd":0.079248,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"NDC80 in Plasmodium berghei localizes to kinetochores and displays dynamic spatiotemporal changes during proliferation, including highly unusual kinetochore arrangements during sexual stages. A very divergent candidate for the SPC24 subunit was identified, completing a canonical NDC80 complex structure in Plasmodium. Live-cell imaging revealed NDC80 as part of the outer kinetochore complex that attaches centromeres to spindle microtubules during atypical endomitosis and endoreduplication.\",\n      \"method\": \"NDC80-GFP live-cell imaging in P. berghei, proteomics/complex composition analysis, identification of divergent SPC24 subunit\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live-cell imaging with functional localization data and complex composition identification in a single lab using multiple methods\",\n      \"pmids\": [\"32501284\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NDC80 fluorescence (together with ChIP-seq) was used to identify SMC2/SMC4 condensin subunit localization to centromeres during early schizogony in P. berghei, confirming NDC80 as a centromere/kinetochore marker at this stage. This establishes NDC80's spatial position at centromeres during endomitotic schizogony.\",\n      \"method\": \"Co-localization of NDC80-GFP with SMC2/SMC4 fluorescent fusions; ChIP-seq to confirm centromeric localization\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — NDC80 used as validated kinetochore/centromere marker with orthogonal ChIP-seq confirmation, single lab\",\n      \"pmids\": [\"32049018\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. falciparum gametocytes, NDC80 (PfNDC80) participates in a non-mitotic hemispindle associated with nuclear microtubule assembly/disassembly at a non-mitotic MTOC embedded in the nuclear membrane, driving nuclear elongation, chromatin reorganization, IMC positioning, and subpellicular microtubule formation. Depolymerization of microtubules with trifluralin disrupted NDC80-associated kinetochore organization, linking NDC80 function to the non-mitotic microtubule machinery in gametocytes.\",\n      \"method\": \"3D electron microscopy, fluorescence imaging of PfNDC80 in gametocytes, microtubule depolymerization with trifluralin\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by fluorescence with functional perturbation (trifluralin), orthogonal 3D EM, single lab\",\n      \"pmids\": [\"36030238\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SAS4, a basal body component in Plasmodium, does NOT associate with NDC80, establishing that NDC80 is specifically part of the nuclear envelope/centriolar plaque MTOC and not part of the cytoplasmic basal body/outer centriolar MTOC in male gametocytes.\",\n      \"method\": \"Co-localization and co-immunoprecipitation/fluorescence assays comparing SAS4 and NDC80 localization in P. berghei male gametocytes\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single negative co-localization result used to delineate NDC80's organelle specificity, single lab, single method\",\n      \"pmids\": [\"35550346\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Conditional disruption of PfNDC80 (along with PfNuf2) in P. falciparum causes aberrant mitotic spindle organisation, loss of CENH3 centromere marker integrity, impaired karyokinesis, and—unexpectedly—disengagement of the centriolar plaque (centrosome equivalent) from the nuclear envelope. This leads to formation of anucleate merozoites, revealing that correct kinetochore/spindle complex assembly is required both for chromosome segregation and for positioning the nascent apical complex.\",\n      \"method\": \"Conditional disruption of PfNDC80, ultrastructure-expansion microscopy, fluorescence imaging of spindle/centromere/apical complex markers\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional genetic disruption with defined cellular phenotypes confirmed by ultrastructure-expansion microscopy and multiple fluorescent markers, peer-reviewed\",\n      \"pmids\": [\"38987258\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Kinesin-5 partially co-localizes with NDC80 during early blood stage schizogony and is closely associated with NDC80 during male gametogony in P. berghei, establishing that NDC80 marks kinetochore/spindle regions with which kinesin-5 associates during nuclear division.\",\n      \"method\": \"Fixed-cell immunofluorescence co-localization of kinesin-5 with NDC80, dual-color live-cell imaging in P. berghei\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-localization only (no biochemical interaction confirmed), single lab, single method for the NDC80-specific finding\",\n      \"pmids\": [\"33154955\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0616200 (NDC80) is a kinetochore component that forms part of the canonical outer kinetochore NDC80 complex (including a divergent SPC24 subunit) in Plasmodium, localizing dynamically to centromeres/kinetochores at the nuclear envelope MTOC during atypical endomitosis and endoreduplication; conditional disruption of PfNDC80 in P. falciparum disrupts spindle organization, centromere integrity, and centriolar plaque attachment to the nuclear envelope, causing failed karyokinesis and anucleate merozoites, while in gametocytes NDC80 participates in a non-mitotic hemispindle that drives nuclear elongation and chromatin reorganization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0616200 (NDC80) is an outer-kinetochore component that couples centromeres to spindle microtubules during the atypical, closed nuclear divisions of Plasmodium [#0, #4]. In P. berghei, NDC80 localizes to kinetochores with dynamic spatiotemporal behavior across proliferative and sexual stages and assembles into a canonical NDC80 complex that includes a highly divergent SPC24 subunit [#0]; it serves as a validated centromere/kinetochore marker, co-positioning with centromeric condensin (SMC2/SMC4) during early schizogony [#1]. NDC80 is a component specifically of the nuclear-envelope-embedded centriolar plaque MTOC rather than the cytoplasmic basal body, as it does not associate with the basal body component SAS4 [#3]. Conditional disruption of PfNDC80 in P. falciparum causes aberrant mitotic spindle organization, loss of CENH3 centromere integrity, and failed karyokinesis, and unexpectedly detaches the centriolar plaque from the nuclear envelope, yielding anucleate merozoites — establishing that correct NDC80/spindle assembly is required both for chromosome segregation and for positioning the nascent apical complex [#4]. Beyond mitosis, in P. falciparum gametocytes NDC80 participates in a non-mitotic hemispindle at a nuclear-membrane MTOC that drives nuclear elongation and chromatin reorganization, and its kinetochore organization depends on intact microtubules [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing whether Plasmodium builds a canonical outer kinetochore, this work placed NDC80 at kinetochores throughout proliferation and identified a divergent SPC24 that completes an NDC80 complex, defining the molecular machinery linking centromeres to spindle microtubules in atypical division.\",\n      \"evidence\": \"NDC80-GFP live-cell imaging and complex-composition proteomics in P. berghei\",\n      \"pmids\": [\"32501284\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct microtubule-binding activity of the NDC80 complex not biochemically reconstituted\",\n        \"Stoichiometry and full subunit composition of the divergent complex not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"By using NDC80 as a validated kinetochore/centromere marker co-localizing with condensin subunits, the study fixed NDC80's spatial position at centromeres during endomitotic schizogony.\",\n      \"evidence\": \"Co-localization of NDC80-GFP with SMC2/SMC4 fusions plus ChIP-seq confirmation in P. berghei\",\n      \"pmids\": [\"32049018\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not test whether NDC80 recruits or depends on condensin\",\n        \"NDC80 role here is inferred as a marker, not directly perturbed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To connect kinetochores to spindle motor activity, kinesin-5 was shown to associate with NDC80-marked regions during schizogony and gametogony, positioning NDC80 near the spindle motor machinery.\",\n      \"evidence\": \"Fixed-cell and dual-color live imaging of kinesin-5 with NDC80 in P. berghei\",\n      \"pmids\": [\"33154955\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Co-localization only; no biochemical or direct interaction demonstrated\",\n        \"Functional dependence between NDC80 and kinesin-5 untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Distinguishing which MTOC NDC80 belongs to, the absence of association with the basal body protein SAS4 assigned NDC80 specifically to the nuclear-envelope centriolar plaque MTOC rather than the cytoplasmic basal body in male gametocytes.\",\n      \"evidence\": \"Comparative co-localization and co-IP of SAS4 vs NDC80 in P. berghei male gametocytes\",\n      \"pmids\": [\"35550346\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Rests on a single negative result, not independently confirmed\",\n        \"Does not define what tethers NDC80 to the centriolar plaque MTOC\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extending NDC80 beyond mitosis, this work showed NDC80 functions in a non-mitotic hemispindle during gametocyte development, linking it to microtubule-dependent nuclear elongation and chromatin reorganization.\",\n      \"evidence\": \"3D electron microscopy, PfNDC80 fluorescence imaging, and trifluralin microtubule depolymerization in P. falciparum gametocytes\",\n      \"pmids\": [\"36030238\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which NDC80 organizes non-mitotic microtubules undefined\",\n        \"Whether the gametocyte NDC80 complex differs in composition from the mitotic one unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Answering what NDC80 is functionally required for, conditional disruption revealed that loss of PfNDC80 disrupts spindle and centromere integrity, blocks karyokinesis, and detaches the centriolar plaque from the nuclear envelope, coupling kinetochore assembly to both chromosome segregation and apical-complex positioning.\",\n      \"evidence\": \"Conditional disruption of PfNDC80 with ultrastructure-expansion microscopy and spindle/centromere/apical marker imaging in P. falciparum\",\n      \"pmids\": [\"38987258\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis of centriolar-plaque tethering to the nuclear envelope not identified\",\n        \"Direct versus indirect contribution of NDC80 to apical complex positioning unresolved\",\n        \"Effect co-attributed with PfNuf2; NDC80-specific separable role not isolated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the divergent Plasmodium NDC80 complex physically binds spindle microtubules and how it is recruited to and tethered at the nuclear-envelope centriolar plaque remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reconstituted microtubule-binding assay for the Plasmodium NDC80 complex\",\n        \"Recruitment/tethering mechanism to the centriolar plaque MTOC unknown\",\n        \"Structural model of the divergent complex lacking\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0000776\", \"supporting_discovery_ids\": [0, 1, 2, 4]},\n      {\"term_id\": \"GO:0000778\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005816\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0051301\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0007080\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"NDC80 complex (with divergent SPC24 subunit)\"\n    ],\n    \"partners\": [\n      \"SPC24 (divergent subunit)\",\n      \"PfNuf2\",\n      \"kinesin-5 (co-localization)\",\n      \"SMC2/SMC4 condensin (centromeric co-localization)\"\n    ],\n    \"other_free_text\": [\n      \"Marks the nuclear-envelope centriolar plaque MTOC and is excluded from the cytoplasmic SAS4-associated basal body MTOC\",\n      \"Functions in a non-mitotic hemispindle during P. falciparum gametocyte nuclear elongation\",\n      \"Disruption detaches the centriolar plaque from the nuclear envelope, producing anucleate merozoites\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0616200","name":null,"product":"kinetochore protein NDC80","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1115700","name":null,"product":"kinetochore protein NDC80","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1133800","name":null,"product":"kinetochore protein NDC80, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NDC80","evaluation":null}