Abstract 1353 Phagosomes maturation and resolution: involvement of adaptor protein complexes
Bibliographic record
Abstract
Macrophages are a diverse group of immune cells that play a major role in eliminating dangerous particles.They do this by recognizing, binding to, and then engulfing these particles through a mechanism called phagocytosis.This multistep process starts with the uptake of the particle and phagosome formation, and phagosomes subsequently mature into phagolysosomes wherein the particle is digested.Phagolysosomes then fragment to recycle membranes and reform lysosomes, ensuring the macrophages can undergo additional rounds of phagosome maturation.This final step of phagocytosis is called phagosome resolution.Even if the first steps have been extensively studied and are now well understood, the mechanisms underlying phagosome resolution remains unclear.Recently, we demonstrated that clathrin, a protein usually characterized by its role in endocytosis at the plasma membrane, is involved in phagosome fragmentation and lysosome reformation.This raised the hypothesis that other membrane fission proteins such as the adaptor proteins (AP) complexes could be involved in the recruitment of clathrin on phagosomes and phagosome resolution.Using transient genetic manipulation in macrophages cell lines to knock-down AP complexes, confocal microscopy and biochemistry, our data revealed a role of the different AP complexes in phagocytosis, from the uptake to phagosome resolution.The phagocytic uptake is reduced when AP-1 or AP-3 are silenced, whereas phagosome maturation is touched with AP-1 silencing.Interestingly, silencing the different AP complexes didn't impact the lysosomal acidification.Both AP-2 and AP-3 silencing influence phagosome resolution, but AP-2 had a stronger effect on clathrin-dependent resolution.Finally, both AP-2 and clathrin localized on the phagosomes.We are currently pursuing the hypothesis of the involvement of a lysosomal protein in the recruitment of AP-2 and subsequently clathrin to induce phagosome fragmentation.Overall, we demonstrated that the different AP complexes are regulating different steps from phagosomes' formation to their resolution.Our last results concerning the understanding of the mechanisms behind phagosome resolution will be presented.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".