Monocyte Differentiation Up-regulates the Expression of the Lysosomal Sialidase, Neu1, and Triggers Its Targeting to the Plasma Membrane via Major Histocompatibility Complex Class II-positive Compartments
Bibliographic record
Abstract
Human sialidase (neuraminidase) Neu1 catalyzes lysosomal catabolism of sialylated glycoconjugates. Here we show that during the differentiation of monocytes and the monocytic cell line, THP-1, into macrophages, the majority of Neu1 relocalizes from the lysosomes to the cell surface. In contrast to other cellular sialidases Neu2, Neu3, and Neu4, whose expression either remains unchanged or is down-regulated, Neu1 mRNA, protein and activity are specifically increased during the phorbol 12-myristate 13-acetate-induced differentiation, consistent with a significant induction of the transcriptional activity of the Neu1 gene promoter. The lysosomal carboxypeptidase, cathepsin A, which forms a complex with and activates Neu1 in the lysosome, is sorted to the plasma membrane of the differentiating cells similarly to Neu1. Both proteins are first targeted to the lysosome and then are sorted to the LAMP-2-negative, major histo-compatibility complex II-positive vesicles, which later merge with the plasma membrane. Similar trafficking was observed for the internalized fluorescent dextran or horseradish peroxidase initially stored in the lysosomal/endosomal compartment. The suppression of Neu1 expression in the THP-1-derived macrophages by small interfering RNA or with anti-Neu1 antibodies significantly reduced the ability of the cells to engulf bacteria or to produce cytokines. Altogether our data suggest that the upregulation of the Neu1 expression is important for the primary function of macrophages and establish the link between Neu1 and the cellular immune response.
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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) | 0.001 | 0.000 |
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".