Correction: Subcellular Localization of Iron and Heme Metabolism Related Proteins at Early Stages of Erythrophagocytosis
Bibliographic record
Abstract
Background: Senescent red blood cells (RBC) are recognized, phagocytosed and cleared by tissue macrophages.During this erythrophagocytosis (EP), RBC are engulfed and processed in special compartments called erythrophagosomes.We previously described that following EP, heme is rapidly degraded through the catabolic activity of heme oxygenase (HO).Extracted heme iron is then either exported or stored by macrophages.However, the cellular localization of the early steps of heme processing and iron extraction during EP remains to be clearly defined. Methodology/Principal Findings:We took advantage of our previously described cellular model of EP, using bone marrowderived macrophages (BMDM).The subcellular localization of both inducible and constitutive isoforms of HO (HO-1 and HO-2), of the divalent metal transporters (Nramp1, Nramp2/DMT1, Fpn), and of the recently identified heme transporter HRG-1, was followed by fluorescence and electron microscopy during the earliest steps of EP.We also looked at some ER [calnexin, glucose-6-phosphatase (G6Pase) activity] and lysosomes (Lamp1) markers during EP.In both quiescent and LPS-activated BMDM, Nramp1 and Lamp1 were shown to be strong markers of the erythrophagolysosomal membrane.HRG-1 was also recruited to the erythrophagosome.Furthermore, we observed calnexin labeling and G6Pase activity at the erythrophagosomal membrane, indicating the contribution of ER in this phagocytosis model.In contrast, Nramp2/DMT1, Fpn, HO-1 and HO-2 were not detected at the membrane of erythrophagosomes.Conclusions/Significance: Our study highlights the subcellular localization of various heme-and iron-related proteins during early steps of EP, thereby suggesting a model for heme catabolism occurring outside the phagosome, with heme likely being transported into the cytosol through HRG1.The precise function of Nramp1 at the phagosomal membrane in this model remains to be determined.
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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 | 0.002 | 0.028 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.004 | 0.006 |
| Insufficient payload (model declined to judge) | 0.063 | 0.021 |
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".