{"id":"e2c8ef00-f1c6-5f11-a7aa-811be79c6e15","stable_key":"research:lrp8-dab1-separation","predicate":"supports","statement":"ApoER2 intracellular-domain mutant experiments separate selenium uptake from its Dab1-associated signaling requirement.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:supported_interpretation","direction":"context_dependent","is_public":true,"mechanism_event_id":"bb5becb4-8ec9-5040-b7a3-30a806d6da37","mechanism_event_label":"Sharing a receptor does not mean uptake requires the same signaling adaptor.","subject":{"id":"f47ee853-9252-56f4-8e2a-48ede17ed3a3","slug":"lrp8","display_name":"ApoER2 / LRP8","entity_type_key":"protein"},"object":{"id":"c9b77137-454d-5da3-aec0-852370f27272","slug":"selenop-tissue-uptake","display_name":"SELENOP uptake in brain and testis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bb5becb4-8ec9-5040-b7a3-30a806d6da37","stable_key":"research:lrp8-dab1-separation","event_type":"contextual_mechanism","label":"Sharing a receptor does not mean uptake requires the same signaling adaptor.","description":"ApoER2 intracellular-domain mutant experiments separate selenium uptake from its Dab1-associated signaling requirement.","status":"active","compartment":null,"participants":[{"entity":{"id":"3df330b8-2c2a-550c-ae73-46fad0af71a7","slug":"dab1","display_name":"DAB1","entity_type_key":"protein"},"role":"signaling_adaptor","stoichiometry":null,"state_label":"not established as required for selenium uptake","sequence_order":0,"notes":""},{"entity":{"id":"f47ee853-9252-56f4-8e2a-48ede17ed3a3","slug":"lrp8","display_name":"ApoER2 / LRP8","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c9b77137-454d-5da3-aec0-852370f27272","slug":"selenop-tissue-uptake","display_name":"SELENOP uptake in brain and testis","entity_type_key":"cellular_process"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Brain and testis tissue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"ApoER2 domain-mutant mice; brain/testis selenium assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not rule out every possible cross-talk or competition mechanism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"991bf7ea-3b92-5559-9727-fad1408a7c67","evidence_kind":"curated_literature_summary","locator":"lines 1468-1478","start_line":1468,"end_line":1478,"excerpt":"## lrp8-dab1-separation\n\nSharing a receptor does not mean uptake requires the same signaling adaptor.\n\nApoER2 intracellular-domain mutant experiments separate selenium uptake from its Dab1-associated signaling requirement.\n\nOrganism: Mus musculus\nCell type: Brain and testis tissue\nExperimental model: ApoER2 domain-mutant mice; brain/testis selenium assays\nLimitations: Does not rule out every possible cross-talk or competition mechanism.\nPrimary reference: [Differential Functions of the Apoer2 Intracellular Domain in Selenium Uptake and Cell Signaling](https://pmc.ncbi.nlm.nih.gov/articles/PMC2642607/)","model_system":"ApoER2 domain-mutant mice; brain/testis selenium assays","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"4657969d-4d40-57d5-9ea0-439ffa2374bf","title":"Shared ApoER2 does not imply shared Dab1 dependence","kind":"qualification","status":"qualified","why":"Mouse receptor-domain experiments separate selenium delivery from the Dab1-associated signaling requirement asserted as shared.","resolution":"Keep SELENOP uptake and Reelin signaling distinct; competition/cross-talk needs its own evidence.","created_at":"2026-09-17 07:19:34","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/4657969d-4d40-57d5-9ea0-439ffa2374bf","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1718,"end_line":1723,"papers":[{"paper_key":"masiulis-2009","title":"Differential Functions of the Apoer2 Intracellular Domain in Selenium Uptake and Cell Signaling","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2642607/","doi":"10.1515/BC.2009.011","year":2009,"model":"ApoER2 domain-mutant mice; brain/testis selenium assays","summary":"Dab1 signaling-domain and selenium-uptake requirements are separable."}]},"sides":[{"conflict_id":"4657969d-4d40-57d5-9ea0-439ffa2374bf","ordinal":0,"label":"Original preserved statement","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":119,"end_line":119,"quote":"**The dream-angle thing:** ApoER2 is also the **Reelin receptor**. Selenium delivery and Reelin neurodevelopmental signaling converge on the same receptor, same Dab1 adaptor. Nobody has properly resolved whether they compete, cross-talk, or gate each other. That's an open door.","claim_id":null,"source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":[]},{"conflict_id":"4657969d-4d40-57d5-9ea0-439ffa2374bf","ordinal":1,"label":"Original preserved statement","revision_id":"4cec6304-35d7-5560-9133-e6ea689db838","start_line":452,"end_line":454,"quote":"ApoER2 is both the **selenium delivery receptor** and the **Reelin receptor**, sharing the **Dab1** adaptor. Reelin lays out cortical lamination. SELENOP delivers the selenium that neurons need to survive. They are competing or cooperating on the same receptor during exactly the same developmental window — and nobody has resolved which.\n\nTestable: does SELENOP occupancy **modulate Reelin-induced Dab1 phosphorylation**? If yes, then **maternal selenium status is a direct input to cortical lamination**, and a whole set of neurodevelopmental associations that currently look like \"selenium is good for the brain\" would have an actual mechanism. And it would retroactively explain the Minamata developmental phenotype from a second direction — mercury sequestering SELENOP means it isn't just failing to deliver selenium, it's failing to reach ApoER2 during lamination.","claim_id":null,"source_key":"corrections","source_title":"Selenium corrections and deep dive","claim_ids":[]},{"conflict_id":"4657969d-4d40-57d5-9ea0-439ffa2374bf","ordinal":2,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1718,"end_line":1723,"quote":"## Shared ApoER2 does not imply shared Dab1 dependence\n\nMouse receptor-domain experiments separate selenium delivery from the Dab1-associated signaling requirement asserted as shared.\n\nKeep SELENOP uptake and Reelin signaling distinct; competition/cross-talk needs its own evidence.\nPrimary reference: [Differential Functions of the Apoer2 Intracellular Domain in Selenium Uptake and Cell Signaling](https://pmc.ncbi.nlm.nih.gov/articles/PMC2642607/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"Sharing a receptor does not mean uptake requires the same signaling adaptor.","evidence_scope":"supported_interpretation","papers":[{"key":"masiulis-2009","title":"Differential Functions of the Apoer2 Intracellular Domain in Selenium Uptake and Cell Signaling","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2642607/","doi":"10.1515/BC.2009.011","year":2009,"model":"ApoER2 domain-mutant mice; brain/testis selenium assays","summary":"Dab1 signaling-domain and selenium-uptake requirements are separable."}]}}