{"id":"ae018f32-d031-50ba-a0f1-6d10b352b30a","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-brain-transporter-loss","predicate":"regulates","statement":"Slc6a20a-knockout mice had higher extracellular brain glycine and increased NMDA-receptor currents.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ffbe3849-b106-532c-a097-eb699493858c","mechanism_event_label":"Changing a proline-sharing transporter can change glycine-dependent brain signaling.","subject":{"id":"30ebc6a1-4083-563e-b5a8-0417abd0b173","slug":"mouse-slc6a20a","display_name":"Mouse sodium/imino-acid transporter / Slc6a20a","entity_type_key":"protein"},"object":{"id":"2b507258-430c-51fe-9fd2-e510c2c197a9","slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"ffbe3849-b106-532c-a097-eb699493858c","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-brain-transporter-loss-event","event_type":"observed_relationship","label":"Changing a proline-sharing transporter can change glycine-dependent brain signaling.","description":"Slc6a20a-knockout mice had higher extracellular brain glycine and increased NMDA-receptor currents.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"30ebc6a1-4083-563e-b5a8-0417abd0b173","slug":"mouse-slc6a20a","display_name":"Mouse sodium/imino-acid transporter / Slc6a20a","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2b507258-430c-51fe-9fd2-e510c2c197a9","slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse genetic deletion with extracellular amino-acid measurements and electrophysiology.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This does not show that oral proline treats NMDAR dysfunction in humans. Correction record: Author correction PMID 39242973 / DOI 10.1038/s44321-024-00125-y corrects the human embryonic stem-cell neuron protocol IRB approval number to KH2017-109 from KA2018-61 and KH2020-55. It does not report a change to experimental results. https://link.springer.com/article/10.1038/s44321-024-00125-y","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Changing a proline-sharing transporter can change glycine-dependent brain signaling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33428810/ · DOI 10.15252/emmm.202012632","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1c8f8b81-3caa-55ff-8f32-98a00f363c30","evidence_kind":"source_excerpt","locator":"Lines 206-212","start_line":206,"end_line":212,"excerpt":"## l-proline-brain-transporter-loss\nChanging a proline-sharing transporter can change glycine-dependent brain signaling.\nSlc6a20a-knockout mice had higher extracellular brain glycine and increased NMDA-receptor currents.\nModel: Mouse genetic deletion with extracellular amino-acid measurements and electrophysiology.\nLimitations: This does not show that oral proline treats NMDAR dysfunction in humans. Correction record: Author correction PMID 39242973 / DOI 10.1038/s44321-024-00125-y corrects the human embryonic stem-cell neuron protocol IRB approval number to KH2017-109 from KA2018-61 and KH2020-55. It does not report a change to experimental results. https://link.springer.com/article/10.1038/s44321-024-00125-y\nEvidence access: Primary full text\nSLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33428810/ · DOI 10.15252/emmm.202012632","model_system":"Mouse genetic deletion with extracellular amino-acid measurements and electrophysiology.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e5aa7fc5-ee52-5376-8169-416082a89fd1","stable_key":"import-6612c190-1948-5bcf-bbe3-a7f6c50fa3cf","title":"L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"7b7f1981f9c7897fbb6baa19425bdc19dede78ad4d66fa554394b8337c7366fb","revision_id":"4971a925-fa70-59f8-8030-d3029a18a62f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}