{"gene":"PF3D7_0822500","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2010,"finding":"PfDLC1 (PF3D7_0822500) physically interacts with P. falciparum myosin A and actin 1, as demonstrated by co-immunoprecipitation experiments. The interacting domains were mapped to sequences containing SDIE and/or EEMKT motifs in the upper 50-kDa segment of the myosin A head domain, and to subdomain IV of actin 1.","method":"Co-immunoprecipitation and interaction domain mapping","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with domain mapping, single lab, two orthogonal methods (Co-IP plus domain-mapping experiments)","pmids":["20421304"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"PfDLC1 (PF3D7_0822500) localises to the cytoplasm in a pattern similar to actin, and co-localises with myosin A by immunofluorescence, consistent with its interaction with the actin/myosin machinery in blood-stage parasites.","method":"Fluorescence tagging and immunofluorescence microscopy","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment corroborated by co-IP, single lab","pmids":["20421304"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Attempts to disrupt the dlc1 gene by reverse genetics in both P. falciparum and P. berghei were unsuccessful, suggesting DLC1 (PF3D7_0822500) is essential for blood-stage parasite survival or its locus is inaccessible.","method":"Reverse genetic disruption attempts (negative result — gene could not be knocked out)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — attempted in two Plasmodium species with consistent failure, single lab","pmids":["20421304"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"finding":"DLC1 (PF3D7_0822500) protein is expressed at high levels in late trophozoites and schizonts, indicating a role in blood-stage development in the absence of flagella.","method":"Expression analysis (Western blot / protein detection across blood stages)","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (protein expression profiling), no direct functional consequence established","pmids":["20421304"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"In P. berghei male gametocytes, loss of the RNA-binding protein RBPm1 causes intron retention in dlc1 (ortholog of PF3D7_0822500) and consequent loss of DLC1 protein expression, placing DLC1 as a downstream target of the RBPm1-dependent axonemal intron-splicing program required for male gametogenesis.","method":"RNA-seq (intron retention analysis), RT-PCR confirmation, and immunoblot/IFA of HA-tagged endogenous DLC1 protein in RBPm1-null parasites","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (RNA-seq, RT-PCR, protein tagging/IFA, immunoblot) in single study; finding is about post-transcriptional regulation of DLC1 rather than DLC1's own enzymatic mechanism","pmids":["38824128"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"17XNL"}]}],"current_model":"PF3D7_0822500 (DLC1), a leucine-rich repeat dynein light chain, is expressed in blood-stage P. falciparum (late trophozoites/schizonts) where it localises to the cytoplasm and physically interacts with myosin A (via SDIE/EEMKT motifs in the motor head) and actin 1 (via subdomain IV), implicating it in the actin–myosin machinery essential for erythrocytic development; attempts to knock out dlc1 in P. falciparum and P. berghei failed, suggesting essentiality; and in P. berghei male gametocytes, DLC1 protein expression depends on RBPm1-mediated splicing of a retained intron within the dlc1 transcript, placing it within an axonemal intron-splicing program required for male gametogenesis."},"narrative":{"mechanistic_narrative":"PF3D7_0822500 (DLC1) is a dynein light chain implicated in the actin–myosin motility machinery of Plasmodium blood-stage parasites [PMID:20421304]. In P. falciparum, DLC1 physically interacts with both myosin A and actin 1, with binding mapped to SDIE/EEMKT motifs in the upper 50-kDa segment of the myosin A head domain and to subdomain IV of actin 1 [PMID:20421304], and it co-localises with actin and myosin A in the parasite cytoplasm [PMID:20421304]. Attempts to disrupt dlc1 by reverse genetics failed in both P. falciparum and P. berghei, consistent with essentiality for blood-stage survival [PMID:20421304]. In P. berghei male gametocytes, DLC1 protein expression additionally depends on RBPm1-mediated splicing of a retained intron in the dlc1 transcript, placing DLC1 as a downstream target of an axonemal intron-splicing program required for male gametogenesis [PMID:38824128]. Beyond these interaction, localisation, and regulatory findings, the enzymatic or motor-regulatory function of DLC1 itself has not been characterized in the available corpus.","teleology":[{"year":2010,"claim":"To determine what DLC1 does in a parasite lacking flagella, its physical partners were sought, establishing DLC1 as a binding component of the actin–myosin machinery rather than a canonical axonemal dynein light chain.","evidence":"Reciprocal co-immunoprecipitation with interaction-domain mapping in P. falciparum","pmids":["20421304"],"confidence":"Medium","gaps":["Does not establish whether DLC1 regulates myosin A motor activity or actin dynamics functionally","Binding shown by Co-IP in a single lab without structural or reconstitution data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"To test whether the interaction data reflect a genuine cellular association, DLC1 subcellular distribution was examined, showing cytoplasmic co-localisation with actin and myosin A consistent with the biochemical partnerships.","evidence":"Fluorescence tagging and immunofluorescence microscopy in blood-stage P. falciparum","pmids":["20421304"],"confidence":"Medium","gaps":["Co-localisation does not resolve spatial dynamics during invasion or replication","Does not distinguish direct from indirect association in vivo"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"To assess biological importance, gene disruption was attempted; the consistent failure to knock out dlc1 across two Plasmodium species argued for essentiality in blood-stage parasites.","evidence":"Reverse-genetic disruption attempts (negative result) in P. falciparum and P. berghei","pmids":["20421304"],"confidence":"Medium","gaps":["Failed knockout cannot formally distinguish essentiality from locus inaccessibility","No conditional depletion to define the essential process"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2010,"claim":"Stage-resolved expression profiling addressed when DLC1 acts, showing peak protein levels in late trophozoites and schizonts.","evidence":"Protein expression profiling across blood stages in P. falciparum","pmids":["20421304"],"confidence":"Low","gaps":["Single-method expression profile with no direct functional consequence established","Does not link stage-specific expression to a defined developmental step"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"To explain how DLC1 is controlled during sexual development, its transcript processing was examined, revealing that RBPm1-dependent splicing of a retained intron is required for DLC1 protein production in male gametocytes.","evidence":"RNA-seq intron-retention analysis, RT-PCR, and immunoblot/IFA of HA-tagged endogenous DLC1 in RBPm1-null P. berghei","pmids":["38824128"],"confidence":"Medium","gaps":["Concerns post-transcriptional regulation of DLC1, not DLC1's own molecular mechanism","Does not define DLC1's role within the male gametogenesis axoneme"],"attribution":[{"species":"Plasmodium berghei","strain":"17XNL"}]},{"year":null,"claim":"It remains unknown how DLC1 mechanistically influences the actin–myosin motor (e.g., whether it modulates myosin A activity or actin architecture) and what specific essential blood-stage process it supports.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No conditional depletion phenotype defining the essential function","No structural or in vitro reconstitution of DLC1–myosin A–actin interactions","Role in the male gametogenesis axoneme not directly assayed"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MYOSIN A (P. FALCIPARUM) [#0]","ACTIN 1 (P. FALCIPARUM) [#0]","RBPM1 (P. BERGHEI) — REGULATOR OF DLC1 SPLICING, NOT A PHYSICAL PARTNER OF DLC1 PROTEIN [#4]"],"other_free_text":["DLC1 interaction with myosin A maps to SDIE/EEMKT motifs in the upper 50-kDa segment of the myosin A head domain, and to subdomain IV of actin 1 [#0].","Peak DLC1 protein expression occurs in late trophozoites and schizonts [#3].","dlc1 could not be disrupted in P. falciparum or P. berghei, consistent with essentiality [#2].","In P. berghei male gametocytes, DLC1 protein requires RBPm1-mediated splicing of a retained intron in the dlc1 transcript [#4]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"20421304","id":"PMC_20421304","title":"Plasmodium falciparum dynein light chain 1 interacts with actin/myosin during blood stage development.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20421304","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DLC1","dynein light chain 1","PfDLC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38824128","id":"","title":"An axonemal intron splicing program sustains Plasmodium male development.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38824128","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DLC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4806,"output_tokens":1444,"usd":0.018039,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6367,"output_tokens":2459,"usd":0.046655,"stage2_stop_reason":"end_turn"},"total_usd":0.064694,"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\": 2010,\n      \"finding\": \"PfDLC1 (PF3D7_0822500) physically interacts with P. falciparum myosin A and actin 1, as demonstrated by co-immunoprecipitation experiments. The interacting domains were mapped to sequences containing SDIE and/or EEMKT motifs in the upper 50-kDa segment of the myosin A head domain, and to subdomain IV of actin 1.\",\n      \"method\": \"Co-immunoprecipitation and interaction domain mapping\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with domain mapping, single lab, two orthogonal methods (Co-IP plus domain-mapping experiments)\",\n      \"pmids\": [\"20421304\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PfDLC1 (PF3D7_0822500) localises to the cytoplasm in a pattern similar to actin, and co-localises with myosin A by immunofluorescence, consistent with its interaction with the actin/myosin machinery in blood-stage parasites.\",\n      \"method\": \"Fluorescence tagging and immunofluorescence microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment corroborated by co-IP, single lab\",\n      \"pmids\": [\"20421304\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Attempts to disrupt the dlc1 gene by reverse genetics in both P. falciparum and P. berghei were unsuccessful, suggesting DLC1 (PF3D7_0822500) is essential for blood-stage parasite survival or its locus is inaccessible.\",\n      \"method\": \"Reverse genetic disruption attempts (negative result — gene could not be knocked out)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — attempted in two Plasmodium species with consistent failure, single lab\",\n      \"pmids\": [\"20421304\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"DLC1 (PF3D7_0822500) protein is expressed at high levels in late trophozoites and schizonts, indicating a role in blood-stage development in the absence of flagella.\",\n      \"method\": \"Expression analysis (Western blot / protein detection across blood stages)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (protein expression profiling), no direct functional consequence established\",\n      \"pmids\": [\"20421304\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In P. berghei male gametocytes, loss of the RNA-binding protein RBPm1 causes intron retention in dlc1 (ortholog of PF3D7_0822500) and consequent loss of DLC1 protein expression, placing DLC1 as a downstream target of the RBPm1-dependent axonemal intron-splicing program required for male gametogenesis.\",\n      \"method\": \"RNA-seq (intron retention analysis), RT-PCR confirmation, and immunoblot/IFA of HA-tagged endogenous DLC1 protein in RBPm1-null parasites\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (RNA-seq, RT-PCR, protein tagging/IFA, immunoblot) in single study; finding is about post-transcriptional regulation of DLC1 rather than DLC1's own enzymatic mechanism\",\n      \"pmids\": [\"38824128\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"17XNL\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0822500 (DLC1), a leucine-rich repeat dynein light chain, is expressed in blood-stage P. falciparum (late trophozoites/schizonts) where it localises to the cytoplasm and physically interacts with myosin A (via SDIE/EEMKT motifs in the motor head) and actin 1 (via subdomain IV), implicating it in the actin–myosin machinery essential for erythrocytic development; attempts to knock out dlc1 in P. falciparum and P. berghei failed, suggesting essentiality; and in P. berghei male gametocytes, DLC1 protein expression depends on RBPm1-mediated splicing of a retained intron within the dlc1 transcript, placing it within an axonemal intron-splicing program required for male gametogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0822500 (DLC1) is a dynein light chain implicated in the actin–myosin motility machinery of Plasmodium blood-stage parasites [#0]. In P. falciparum, DLC1 physically interacts with both myosin A and actin 1, with binding mapped to SDIE/EEMKT motifs in the upper 50-kDa segment of the myosin A head domain and to subdomain IV of actin 1 [#0], and it co-localises with actin and myosin A in the parasite cytoplasm [#1]. Attempts to disrupt dlc1 by reverse genetics failed in both P. falciparum and P. berghei, consistent with essentiality for blood-stage survival [#2]. In P. berghei male gametocytes, DLC1 protein expression additionally depends on RBPm1-mediated splicing of a retained intron in the dlc1 transcript, placing DLC1 as a downstream target of an axonemal intron-splicing program required for male gametogenesis [#4]. Beyond these interaction, localisation, and regulatory findings, the enzymatic or motor-regulatory function of DLC1 itself has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"To determine what DLC1 does in a parasite lacking flagella, its physical partners were sought, establishing DLC1 as a binding component of the actin–myosin machinery rather than a canonical axonemal dynein light chain.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation with interaction-domain mapping in P. falciparum\",\n      \"pmids\": [\"20421304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not establish whether DLC1 regulates myosin A motor activity or actin dynamics functionally\", \"Binding shown by Co-IP in a single lab without structural or reconstitution data\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"To test whether the interaction data reflect a genuine cellular association, DLC1 subcellular distribution was examined, showing cytoplasmic co-localisation with actin and myosin A consistent with the biochemical partnerships.\",\n      \"evidence\": \"Fluorescence tagging and immunofluorescence microscopy in blood-stage P. falciparum\",\n      \"pmids\": [\"20421304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-localisation does not resolve spatial dynamics during invasion or replication\", \"Does not distinguish direct from indirect association in vivo\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"To assess biological importance, gene disruption was attempted; the consistent failure to knock out dlc1 across two Plasmodium species argued for essentiality in blood-stage parasites.\",\n      \"evidence\": \"Reverse-genetic disruption attempts (negative result) in P. falciparum and P. berghei\",\n      \"pmids\": [\"20421304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Failed knockout cannot formally distinguish essentiality from locus inaccessibility\", \"No conditional depletion to define the essential process\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Stage-resolved expression profiling addressed when DLC1 acts, showing peak protein levels in late trophozoites and schizonts.\",\n      \"evidence\": \"Protein expression profiling across blood stages in P. falciparum\",\n      \"pmids\": [\"20421304\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single-method expression profile with no direct functional consequence established\", \"Does not link stage-specific expression to a defined developmental step\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To explain how DLC1 is controlled during sexual development, its transcript processing was examined, revealing that RBPm1-dependent splicing of a retained intron is required for DLC1 protein production in male gametocytes.\",\n      \"evidence\": \"RNA-seq intron-retention analysis, RT-PCR, and immunoblot/IFA of HA-tagged endogenous DLC1 in RBPm1-null P. berghei\",\n      \"pmids\": [\"38824128\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Concerns post-transcriptional regulation of DLC1, not DLC1's own molecular mechanism\", \"Does not define DLC1's role within the male gametogenesis axoneme\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"17XNL\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how DLC1 mechanistically influences the actin–myosin motor (e.g., whether it modulates myosin A activity or actin architecture) and what specific essential blood-stage process it supports.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No conditional depletion phenotype defining the essential function\", \"No structural or in vitro reconstitution of DLC1–myosin A–actin interactions\", \"Role in the male gametogenesis axoneme not directly assayed\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0045502\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0051015\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007018\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0048232\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Myosin A (P. falciparum) [#0]\",\n      \"Actin 1 (P. falciparum) [#0]\",\n      \"RBPm1 (P. berghei) — regulator of dlc1 splicing, not a physical partner of DLC1 protein [#4]\"\n    ],\n    \"other_free_text\": [\n      \"DLC1 interaction with myosin A maps to SDIE/EEMKT motifs in the upper 50-kDa segment of the myosin A head domain, and to subdomain IV of actin 1 [#0].\",\n      \"Peak DLC1 protein expression occurs in late trophozoites and schizonts [#3].\",\n      \"dlc1 could not be disrupted in P. falciparum or P. berghei, consistent with essentiality [#2].\",\n      \"In P. berghei male gametocytes, DLC1 protein requires RBPm1-mediated splicing of a retained intron in the dlc1 transcript [#4].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0822500","name":null,"product":"dynein light chain 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0708100","name":null,"product":"dynein light chain 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1316500","name":null,"product":"dynein light chain 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"DLC1","evaluation":null}