OC 18.4 Actin Bundling Protein L-Plastin Regulates Platelet Spreading and Thrombosis
Bibliographic record
Abstract
Background: Physiologically resting platelets circulate in the blood in discoid shape.Upon vascular injury or during thrombosis, platelets become activated, extend filopodia, spread and expand surface area, aggregate and form thrombi, which relies on dynamic F-actin disassembly and reassembly.Although several actin-binding proteins in platelets have been identified, largely remain unknown.L-plastin, an actin bundling protein, has not been studied in platelets.It is predicted with two C-terminal actin binding domains that can cross-link actin filaments.It is critical for immunity, adhesion, and migration in leukocytes.We recently found it critical in maintaining megakaryocyte cytoskeleton stiffness and inhibits platelet production.Aims: We aim to study the role of L-plastin in platelet cytoskeleton change, activation and thrombosis.Methods: Platelets or whole blood from L-plastin deficiency mice (Lcp1KO) and litlermate controls (WT) were used for in vitro assays.The collagen/ epinephrine induced pulmonary embolism (PE) model was used for in vivo thrombosis evaluation.Results: When stimulated with different concentrations of thrombin or 2MeSADP, platelets from both WT and KO mice expressed JONA and Pselectin without significant difference.This suggests that L-plastin does not alter early inside-out signaling pathway.When we measured the platelet spreading on immobilized fibrinogen, KO platelets showed significantly enlarged actin spreading area per platelet as compared to the WT (n = 3, P < 0.05), suggesting that L-plastin inhibits platelet spreading through outside-in signaling.Platelets from KO mice also have accelerated clot retraction.In addition, microfluidics assay using DiOC6 labelled whole blood showed accelerated adhesion to both collagen and fibrinogen immobilized matrixes under a shear stress of 200/s in the KO group (n = 4, p < 0.05).In the PE model, KO mice showed significantly accelerated mortality (n = 8-9, P < 0.01), suggesting an inhibitory role of L-plastin in thrombosis in vivo. Conclusion(s):In summary, we found an inhibitory role of L-plastin in platelet spreading in vitro and thrombosis in vivo.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".