{"id":"737cb58c-622a-5bf1-bb79-24998d11f96f","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-megalin-retrieval","predicate":"mediates_reclamation","statement":"Megalin-mediated endocytosis retrieved filtered vitamin D-binding-protein/calcifediol complexes in proximal tubules.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"67dd4e83-49fa-5e69-ad11-7df468d1ece1","mechanism_event_label":"Kidney cells reclaim carrier-bound D3 precursor from the filtrate.","subject":{"id":"249ecc7c-b115-508f-acda-94c954e5cd2b","slug":"mouse-lrp2","display_name":"Mouse megalin / Lrp2","entity_type_key":"protein"},"object":{"id":"76158c18-7aae-5079-bcfd-b0aeb7e272f6","slug":"renal-calcifediol-reclamation","display_name":"Renal reclamation of filtered calcifediol","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"67dd4e83-49fa-5e69-ad11-7df468d1ece1","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-megalin-retrieval-event","event_type":"biochemical_relationship","label":"Kidney cells reclaim carrier-bound D3 precursor from the filtrate.","description":"Megalin-mediated endocytosis retrieved filtered vitamin D-binding-protein/calcifediol complexes in proximal tubules.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"249ecc7c-b115-508f-acda-94c954e5cd2b","slug":"mouse-lrp2","display_name":"Mouse megalin / Lrp2","entity_type_key":"protein"},"role":"endocytic_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0c858f70-5b07-5db5-8494-bfe3d8733b34","slug":"mouse-gc","display_name":"Mouse vitamin D-binding protein / Gc","entity_type_key":"protein"},"role":"carrier","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6bd73bd2-1f0a-5caa-ba69-7ce1b75364bb","slug":"calcifediol","display_name":"Calcifediol / 25-hydroxyvitamin D3","entity_type_key":"small_molecule"},"role":"cargo","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"76158c18-7aae-5079-bcfd-b0aeb7e272f6","slug":"renal-calcifediol-reclamation","display_name":"Renal reclamation of filtered calcifediol","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary abstract, receptor-mediated uptake and knockout phenotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse renal endocytosis experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Endogenous carrier complexes and uptake assays; timing not specified in abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Renal endocytosis finding does not exclude free-hormone uptake elsewhere.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Vitamin D2 and D3","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"nutrient_topic","value_text":"Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Kidney cells reclaim carrier-bound D3 precursor from the filtrate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"kidney proximal tubule","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b776d624-c008-58c7-a7ae-032c9ee89aff","evidence_kind":"source_excerpt","locator":"Lines 227-240","start_line":227,"end_line":240,"excerpt":"### vd-act-megalin-retrieval\nMegalin-mediated endocytosis retrieved filtered vitamin D-binding-protein/calcifediol complexes in proximal tubules.\nCondition category: normal\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Kidney cells reclaim carrier-bound D3 precursor from the filtrate.\norganism: Mus musculus\ntissue_or_cell_type: kidney proximal tubule\nexperimental_model: Mouse renal endocytosis experiments\nlimitations: Renal endocytosis finding does not exclude free-hormone uptake elsewhere.\nexposure: Endogenous carrier complexes and uptake assays; timing not specified in abstract.\ncross_nutrient: false\nevidence_location: Primary abstract, receptor-mediated uptake and knockout phenotype.\nnutrient: Vitamin D2 and D3\n[nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8","model_system":"Mouse renal endocytosis experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [nykjaer1999] An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. (1999). https://pubmed.ncbi.nlm.nih.gov/10052453/ DOI: 10.1016/s0092-8674(00)80655-8","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c95c763c-5b31-5b3f-a2f8-2dfe5ef0d3ca","stable_key":"import-1deb434a-3547-51a0-a038-87b1ce79ec38","title":"Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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