{"id":"dae6dcf0-4c7d-518c-93ca-9ac1f851b8f9","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-only-particles-signal","predicate":"enables","statement":"Despite its ability to bind both soluble and particulate beta-glucan polymers, Dectin-1 signalling is only activated by particulate beta-glucans, which cluster the receptor in synapse-like structures from which the regulatory tyrosine phosphatases CD45 and CD148 are excluded, providing a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance and initiate direct cellular antimicrobial responses only when they are required.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"8d0ac361-0382-59b0-8f6e-d62f8a8c383f","mechanism_event_label":"Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.","subject":{"id":"85151d5b-ac26-513a-96b2-4e3a9d25f453","slug":"phagocytic-synapse","display_name":"The phagocytic synapse, a receptor-rich contact that excludes CD45 and CD148","entity_type_key":"cellular_process"},"object":{"id":"117c178c-d74c-5c56-b2d6-d3956ad70c03","slug":"clec7a","display_name":"Dectin-1 / CLEC7A","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"8d0ac361-0382-59b0-8f6e-d62f8a8c383f","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-only-particles-signal-event","event_type":"biochemical_relationship","label":"Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.","description":"Despite its ability to bind both soluble and particulate beta-glucan polymers, Dectin-1 signalling is only activated by particulate beta-glucans, which cluster the receptor in synapse-like structures from which the regulatory tyrosine phosphatases CD45 and CD148 are excluded, providing a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance and initiate direct cellular antimicrobial responses only when they are required.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f1d38046-6772-515b-9276-9b38748ae601","slug":"ptprc","display_name":"PTPRC","entity_type_key":"protein"},"role":"excluded_phosphatase","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a19e0ed5-8f50-57c8-8a8a-968221851923","slug":"ptprj","display_name":"Receptor-type tyrosine-protein phosphatase eta / CD148","entity_type_key":"protein"},"role":"excluded_phosphatase","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ee7d7fb7-f994-5c38-8473-6305a63f455f","slug":"phagocytosis","display_name":"Phagocytosis","entity_type_key":"cellular_process"},"role":"associated_response","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b51f3150-efc0-5413-a47a-01d094d248b7","slug":"reactive-oxygen-species","display_name":"Reactive oxygen species","entity_type_key":"chemical_species"},"role":"downstream_output","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"85151d5b-ac26-513a-96b2-4e3a9d25f453","slug":"phagocytic-synapse","display_name":"The phagocytic synapse, a receptor-rich contact that excludes CD45 and CD148","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"117c178c-d74c-5c56-b2d6-d3956ad70c03","slug":"clec7a","display_name":"Dectin-1 / CLEC7A","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glucan-research/21525931.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0\", \"start_char\": 0, \"end_char\": 1406, \"text_sha256\": \"5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Soluble against particulate beta-glucan polymers on Dectin-1-expressing phagocytes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The abstract reports the soluble-versus-particulate comparison and the phosphatase exclusion. It does not state what happens when a soluble glucan is immobilised, so no claim here rests on that.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair.","comparator":null,"unit":null,"notes":"","entity":{"slug":"beta-glucan","display_name":"Beta-glucan","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[bg-p21525931] Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. (2011). https://pubmed.ncbi.nlm.nih.gov/21525931/ DOI: 10.1038/nature10071","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Myeloid phagocytes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0ae2b46a-e4ee-5752-b7e9-28214c194394","evidence_kind":"source_excerpt","locator":"Lines 138-149","start_line":138,"end_line":149,"excerpt":"### bg-only-particles-signal\nDespite its ability to bind both soluble and particulate beta-glucan polymers, Dectin-1 signalling is only activated by particulate beta-glucans, which cluster the receptor in synapse-like structures from which the regulatory tyrosine phosphatases CD45 and CD148 are excluded, providing a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance and initiate direct cellular antimicrobial responses only when they are required.\nCondition category: normal\nnutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair.\nplain_language: Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.\norganism: Mouse\ntissue_or_cell_type: Myeloid phagocytes\nexperimental_model: Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution\nlimitations: The abstract reports the soluble-versus-particulate comparison and the phosphatase exclusion. It does not state what happens when a soluble glucan is immobilised, so no claim here rests on that.\nexposure: Soluble against particulate beta-glucan polymers on Dectin-1-expressing phagocytes\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/21525931.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0\", \"start_char\": 0, \"end_char\": 1406, \"text_sha256\": \"5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0\"}\n[bg-p21525931] Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. (2011). https://pubmed.ncbi.nlm.nih.gov/21525931/ DOI: 10.1038/nature10071","model_system":"Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [bg-p21525931] Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. (2011). https://pubmed.ncbi.nlm.nih.gov/21525931/ DOI: 10.1038/nature10071","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"74dc223d-8289-57bf-a731-d220fa017c1e","stable_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","title":"Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"7c62f2d2f8d99b650e6dc26a505b0f053ae1c8bdb38099d4dfc0771f65287461","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"890ab777-9093-59d9-883f-360e8f80ac19","title":"Is it being particulate that lets a glucan signal through Dectin-1, or is it conformation?","kind":"qualification","status":"open","why":"The phagocytic synapse study is unambiguous within its own design: Dectin-1 bound both soluble and particulate polymers but only particulate ones produced a signal, and the mechanism offered is that particles cluster the receptor into a contact that excludes the CD45 and CD148 phosphatases. A later study of defined fungal glucans reframes the variable. There, glucans of similar Dectin-1 affinity differed in agonistic potential according to how much helical structure they held in solution, denaturation removed the agonism without changing the affinity, and receptor aggregation tracked structure content rather than physical state. The two are reconcilable if what a particle supplies is one way of achieving ordered multivalent presentation and a highly structured soluble polymer is another. That reading is a synthesis rather than a measurement. Neither paper tested the preparations of the other, the later work followed a single receptor isoform, and the aggregates it recorded were small clusters of a few receptors rather than the synapse-scale structures of the earlier study.","resolution":"Unresolved; needs review. The defensible statement is that ordered multivalent presentation is what signals, and particulate form is a reliable but not exclusive way to supply it.","created_at":"2026-09-22 23:28:00","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/890ab777-9093-59d9-883f-360e8f80ac19","sides":[{"conflict_id":"890ab777-9093-59d9-883f-360e8f80ac19","ordinal":0,"label":"Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","start_line":138,"end_line":149,"quote":"### bg-only-particles-signal\nDespite its ability to bind both soluble and particulate beta-glucan polymers, Dectin-1 signalling is only activated by particulate beta-glucans, which cluster the receptor in synapse-like structures from which the regulatory tyrosine phosphatases CD45 and CD148 are excluded, providing a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance and initiate direct cellular antimicrobial responses only when they are required.\nCondition category: normal\nnutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair.\nplain_language: Binding was not enough: the receptor only fired when particles packed it into a patch that shut out the enzymes which switch it off.\norganism: Mouse\ntissue_or_cell_type: Myeloid phagocytes\nexperimental_model: Comparison of soluble and particulate beta-glucan polymers on Dectin-1 signalling, with imaging of receptor and phosphatase distribution\nlimitations: The abstract reports the soluble-versus-particulate comparison and the phosphatase exclusion. It does not state what happens when a soluble glucan is immobilised, so no claim here rests on that.\nexposure: Soluble against particulate beta-glucan polymers on Dectin-1-expressing phagocytes\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/21525931.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0\", \"start_char\": 0, \"end_char\": 1406, \"text_sha256\": \"5bb7dfc847efb60e644eeaf672d3277d18bca9c4fc75051c8d568d8e5dc450e0\"}\n[bg-p21525931] Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. (2011). https://pubmed.ncbi.nlm.nih.gov/21525931/ DOI: 10.1038/nature10071","source_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","source_title":"Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22)","claim_ids":["dae6dcf0-4c7d-518c-93ca-9ac1f851b8f9"]},{"conflict_id":"890ab777-9093-59d9-883f-360e8f80ac19","ordinal":1,"label":"What decides whether the receptor fires is the shape the sugar holds in solution, not how tightly it sticks and not whether it dissolves.","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","start_line":151,"end_line":162,"quote":"### bg-structure-not-solubility-signals\nBeta-glucans can adopt solution structures ranging from random coil to insoluble fibre due to tertiary helical and quaternary structure, and despite similar affinity for Dectin-1 the ability of glucans to induce Dectin-1A-mediated signalling correlates with degree of structure, with glucan denaturation experiments showing that glucan structure determines agonistic potential but not receptor binding affinity, while fluorescence measurements provided direct evidence of ligation-induced Dectin-1A aggregation which positively correlated with increasing glucan structure content.\nCondition category: biomarker_context\nnutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair.\nplain_language: What decides whether the receptor fires is the shape the sugar holds in solution, not how tightly it sticks and not whether it dissolves.\norganism: Human receptor in cultured cells\ntissue_or_cell_type: Dectin-1A-expressing cells and Candida cell wall\nexperimental_model: Glucan denaturation, fluorescence measurement of receptor aggregation and diffusion, and fungal particle contact sites\nlimitations: A single-receptor-isoform study using defined glucan conformations. The aggregates observed were small, a few engaged receptors rather than synapse-scale structures.\nexposure: Fungal beta-glucans of low, medium and high molecular weight differing in helical structure content, before and after denaturation\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/37515324.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c5c602f96f0ff319650a47cb53c772df30c0dc267f6e82c46ae51bb5285b6d3f\", \"start_char\": 0, \"end_char\": 1658, \"text_sha256\": \"c5c602f96f0ff319650a47cb53c772df30c0dc267f6e82c46ae51bb5285b6d3f\"}\n[bg-p37515324] Dectin-1 multimerization and signaling depends on fungal β-glucan structure and exposure. (2023). https://pubmed.ncbi.nlm.nih.gov/37515324/ DOI: 10.1016/j.bpj.2023.07.021","source_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","source_title":"Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22)","claim_ids":["7a759a0a-a5b1-5197-906d-b35abc775e48"]}]}],"corrections":[],"research":null}