Talin mediates monocyte α4β1 integrin‐mediated migration, but not chemokine‐triggered α4β1 affinity up‐regulation or adhesion
Bibliographic record
Abstract
α4β1 integrin plays an important role in monocyte adhesion and emigration. Activation by chemokines and chemoattractants is required to increase α4β1 integrin affinity and mediate adhesion to VCAM‐1 expressed by cytokine‐activated endothelium. We investigated the role of talin, a cytoskeletal protein that interacts with integrin cytoplasmic tails, in α4β1 integrin‐dependent functions using formyl peptide receptor‐transfected U937 monocytic cells. fMLP‐induced affinity up‐regulation, measured by binding of soluble LDV‐FITC peptide, was unaffected by siRNA knockdown of talin‐1 or sequestration of talin through expression of a dominant inhibitory talin‐binding fragment of phosphatidylinositol phosphate kinase type I‐90. Similarly, talin‐1 knockdown did not inhibit fMLP or SDF‐1‐stimulated adhesion to VCAM‐1. Talin was however, essential for PMA‐induced adhesion to VCAM‐1, but not PMA‐induced α4β1 integrin affinity up‐regulation. In addition, talin knockdown reduced fMLP‐driven, α4β1 integrin‐dependent chemotactic migration across VCAM‐1 coated filters. These results suggest that talin association with the cytoplasmic tail of α4β1 integrin is not involved in chemokine‐induced affinity changes or adhesion. However, talin plays an important role in α4β1 integrin‐mediated chemotactic migration and PMA‐induced adhesion to VCAM‐1, steps that follow affinity modulation. Funded by CIHR.
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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) | 0.003 | 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".