Interaction of Multimerin 1 with Collagens: Role in Platelet Adhesion
Bibliographic record
Abstract
Abstract Abstract 2207 Multimerin 1 (MMRN1) is a large, homopolymeric adhesive protein stored in platelets and endothelium that binds to activated platelets, endothelial cells and the extracellular matrix after agonist stimulation. MMRN1 supports platelet adhesion by von Willebrand factor (VWF) dependent and independent mechanisms, and also increases platelet adhesion to Horm collagen. Mice deficient in Mmrn1/Snca (α-synuclein) showed defective platelet adhesion to collagen in vitro and in vivo which was corrected by MMRN1. The ability of MMRN1 to support platelet adhesion in vivo and enhance platelet adhesion to collagen ex vivo, led us to explore the molecular basis of MMRN1 interactions with collagen. Solid phase binding assays were used to test MMRN1 binding to human fibril forming collagen (types I, II, III and V) and to types IV and VI collagen. Binding assays were also used to map the MMRN1 binding sites on collagen using collagen peptide toolkits III and II (which has significant similarity to type I collagen). Static adhesion assays were used to test selected collagen peptides for platelet adhesion. Platelet adhesion assays at high shear rates 1500s−1, were used to test the adhesion of washed platelets from normal and VWF-deficient subjects to type I collagen pre-treated or in fluid phase with: BSA (negative control), MMRN1, VWF or their combination. Human collagens types I, II, III and VI (p-values <0.001) but not types IV or V (p-values = 0.84 and 0.09, respectively) supported MMRN1 binding. Peptide toolkits binding studies indicated that MMRN1 bound to a single site on collagen III (peptide III-38) and to two sites on collagen II, with peptide II-9 showing much stronger binding than peptide II-44. Like the VWF binding peptide III-23 (which did not overlap the MMRN1 binding site), peptide III-38 supported platelet adhesion in combination with GFOGER, the peptide with high affinity for platelet α2β1. The possibility that MMRN1 binds to collagen at sites distinct from VWF was supported by the observations that pre-treatment of collagen I matrices, with the combination of MMRN1 and VWF, increased platelet adhesion more than MMRN1 or VWF alone (p-values< 0.001). Moreover, adhesion deficit of VWF-deficient platelets on collagen type I matrix pre-treated with a combination of MMRN1 and VWF was corrected by adding fluid phase VWF but not MMRN1 (p-values < 0.0001). Taken together, our data indicates that MMRN1 binds to different forms of human collagen that support platelet adhesion. As MMRN1 binds to sites on collagen distinct from VWF or integrin α2β1, it may be important for maximizing platelet adhesion at sites of vascular injury. Disclosures: No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".