Rapid formation of ER‐PM contacts during early stages of phagocytosis
Bibliographic record
Abstract
Membrane contact sites (MCS) are specialized structures where the endoplasmic reticulum (ER) and other organelle form come in close proximity (~10–30 nm). Functionally, these regions are thought to serve as hubs for cellular processes such as inter‐organellar exchange of lipids, calcium homeostasis, and the access of phosphatases to substrates. Consequently, the spatial‐temporal organization of these structures will impact numerous cellular functions. The formation of ER plasma membrane (PM) contact sites are controlled by a variety of membrane tether proteins as well as the morphology of the ER. We and others have found that the sub‐plasmalemmal cortical actin cytoskeleton, a mesh‐like network that occupies 100–200 nm below the PM, can also limit the formation of ER‐PM contact sites. Yet, how ER‐PM junctions are regulated in circumstances where cells have extensive cortical actin remodeling is not understood. An example of such cellular process involving dynamic cortical actin re‐arrangement is phagocytosis. Phagocytosis is an actin‐dependent processes used to internalize particulate material (≥0.5 μm) that serves both antimicrobial and homeostatic functions. The role of the ER in phagocytosis has been a matter of much controversy. Electron micrographs of macrophages undergoing phagocytosis revealed the presence of ER in extensive, close contact with the forming phagosome. It is speculated that the role for ER in this context is to form ER‐PM contact sites with the PM. My studies have revealed that during phagocytosis, the disassembly of F‐actin from the base of the phagocytic cup allows for the formation of new ER‐PM contact sites. ER‐PM contacts formed promptly and specifically where the polymerized actin has been cleared. As such I have found that the spatial occupancy of ER‐PM junction increased ~3 fold during phagocytosis. Finally, I identified PTP1B, a tyrosine phosphatase, as one of the ER‐PM contact proteins that may be functionally important during phagocytosis. Support or Funding Information NSERC PGS‐DCIHR Project Grant
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".