Talin autoinhibition is required for normal hemostasis
Bibliographic record
Abstract
The integrin family of extracellular matrix (ECM) adhesion receptors plays a central role in platelet function, including adhesion and aggregation. In resting platelets, integrins exist in a low-affinity state for their ligands, and are activated upon ligand binding to the extracellular domain or binding of cytoplasmic proteins such as talin to the intracellular β-tail. Talin function is regulated through autoinhibition, which reduces its integrin-activating function. A point mutation that blocks talin autoinhibition, Tln1E1770A, therefore increases integrin activation and disrupts cell migration in fibroblasts. Here, we show that talin autoinhibition also plays an important role during hemostasis. Tln1E1770A mutant mice display defective hemostasis when examined using a tail bleeding assay. Furthermore, platelets isolated from Tln1E1770A mice exhibit disrupted aggregation and delayed clot retraction, indicating a defect in integrin signaling. However, integrin activation was not increased in platelets with defective talin autoinhibition, suggesting a different role for talin in platelets, distinct from inside-out integrin signaling. Taken together, our data shows that talin autoinhibition is an important regulatory mechanism in platelets during hemostasis.
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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 | 0.001 |
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".