Talin is required for LFA-1-induced natural killer cell polarization and cytotoxicity (91.1)
Bibliographic record
Abstract
Abstract The purpose of this study is to elucidate the role that the cytoskeletal adaptor protein talin1 plays in the function of the integrin leukocyte function associated antigen-1 (LFA-1) in NK cells. It has been proposed that LFA-1 not only mediates adhesion of NK cells to target cells but is also an important activating receptor for NK cell cytotoxicity. Talin is known to act as a link between integrins and the actin cytoskeleton and to regulate ligand-binding function of LFA-1. We generated NK cells in vitro from talin1 knockout (KO) embryonic stem cells, tested the effects of talin deficiency on these NK cells, and found that talin plays a dual role in NK cell cytotoxicity. First, it is required for LFA-1 mediated adhesion to the target cell. Second, it is required for the accumulation of actin and actin polymerization machinery, including vinculin and WASP, following binding of LFA-1 to its ligand ICAM-1.This LFA-1- and talin-dependent actin accumulation is a critical for further steps leading to NK cell cytotoxicity. Although talin-KO NK cells adhere to target cells in the presence of Mn++, they are unable to kill the prototypic NK target YAC-1. Wild-type, but not talin-KO, NK cells polarize cytotoxic granules following engagement of both LFA-1 and the activating receptor NKG2D. These data show that LFA-1 mediated actin accumulation precedes and is required for subsequent signalling that leads to cytotoxicity. This work is supported by a grant from the Canadian Institutes of Health Research (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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".