PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape
Bibliographic record
Abstract
The architecture of the endoplasmic reticulum (ER) is a key determinant of its function. Its dynamics are linked to those of the cytoskeleton, but our understanding of how this coordination occurs and what its functional relevance is, limited. Here, we report that the unfolded protein response (UPR ER ) transducer EIF2AK3/PERK (eukaryotic translation initiation factor 2-alpha kinase 3/protein kinase R-like endoplasmic reticulum kinase) is essential for acute-stress-induced peripheral redistribution and remodeling of the ER through eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and translation initiation shutdown. PERK-mediated eIF2α phosphorylation can be bypassed by blocking polysome assembly, depleting microtubule (MT)-anchoring ER proteins such as p180/RRBP1 (ribosome-binding protein 1), or disrupting the MT cytoskeleton. Specific disruption of non-centrosomal MTs, but not centrosome depletion, rescues ER redistribution in PERK-deficient cells. Conversely, PERK deficiency stabilizes non-centrosomal MTs against proteasomal degradation, promoting polarized protrusiveness in epithelial cells and neuroblasts. Thus, PERK coordinates ER architecture and homeostasis with cell morphogenesis by coupling ER remodeling and non-centrosomal MT stability and dynamics. • PERK/EIF2AK3 is identified as a regulator of ER architecture remodeling • Translation initiation suppression is required for ER remodeling during stress • Regulation of ER anchoring to non-centrosomal MTs is required for ER remodeling • ER-MT anchoring feeds back onto cell morphology through non-centrosomal MTs Sanchez-Alvarez et al. report that ER anchoring to non-centrosomal microtubules is regulated by PERK translation suppression activity to both enable ER architecture remodeling during stress and modulate back microtubule dynamics by determining their stability. This mechanism thus couples cell polarization and protrusiveness with ER homeostasis.
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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".