mTOR‐dependent selective translation rapidly expands lysosome biogenesis, volume and retention capacity during phagocyte activatio
Bibliographic record
Abstract
The molecular mechanisms that govern and adapt the number, size, morphology and activities of organelles to suit the needs of the many cell types and conditions that these cells may encounter are at the frontier of cell biology. Lysosomes are organelles that degrade cargo from various routes including endocytosis, phagocytosis and autophagy. Lysosomes have also emerged as a signalling platform that senses and integrates stress signals such as nutrient deprivation with regulatory kinase hubs like mTOR and AMPK to modulate metabolic activity. For phagocytes and antigen‐presenting cells like macrophages and dendritic cells, lysosomes are a kingpin organelle since they are essential to kill pathogens, and process and ultimately present antigens. During phagocyte activation with lipopolysaccharides, lysosomes undergo a striking reorganization, changing from dozens of globular objects to a tubular network, in a process that requires the phosphatidylinositol‐3‐kinase‐Akt‐mTOR signalling axis. Ultimately, lysosome tubulation is thought to promote pinocytic retention and antigen presentation. Here, we show that lysosome tubulation is accompanied by a rapid boost in lysosome volume and holding capacity of phagocyte activation. We reveal that lysosome expansion depends on biosynthesis of lysosomal proteins but is independent of TFEB and TFE3, transcription factors known to scale up lysosome biogenesis. Instead, we show that lysosome transcripts are selectively targeted for enhanced protein translation in an mTOR‐dependent manner. Indeed, lysosome transcripts were enriched in polyribosome fractions after lipopolysaccharide exposure in an mTOR‐dependent manner, while transcripts encoding non‐lysosomal proteins were unresponsive to LPS and/or mTOR inhibition. Collectively, we identified an example of rapid organelle expansion and remodelling driven by enhanced and selective protein translation during phagocyte activation. Support or Funding Information Canadian Institutes of Health Research, Canada Research Chair Program, and Ryerson University This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.001 |
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".