Interphase microtubule disassembly is a signaling cue that drives cell rounding at mitotic entry
Bibliographic record
Abstract
ABSTRACT Reorganization of the cortical actin cytoskeleton at mitotic entry is essential to increase membrane tension for cell rounding 1,2 . This spherical shape is necessary for the biogenesis and organization of the mitotic spindle 2-6 . Proteins of the Ezrin, Radixin, Moesin (ERM) family play essential roles in mitotic morphogenesis by linking actomyosin forces to the plasma membrane 2,3,7-10 . While ERMs drive metaphase cell rounding, the cell-cycle signals that prompt their conformational activation in mitosis are unknown 11 . We screened a library of small molecules using novel ERM biosensors 12 and we unexpectedly found that drugs that disassemble microtubules promote ERM activation. Remarkably, cells disassemble their interphase microtubules while entering mitosis 13 . We further discovered that this disassembly of microtubules acts as a cell-cycle signal that directs ERM activation and metaphase cell rounding. We show that GEF-H1, a Rho-GEF inhibited by microtubule binding, acts downstream of microtubule disassembly to activate ERMs via RhoA and its kinase effector SLK. In addition, we demonstrate that GEF-H1 and Ect2, another Rho-GEF responsible for the generation of mitotic actomyosin forces 6,14 , act together to drive metaphase ERM activation and cell rounding. In summary, we report microtubule disassembly as a cell cycle signal that triggers a signaling network ensuring that actomyosin forces are efficiently integrated at the plasma membrane to promote cell rounding at mitotic entry.
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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) | 0.002 | 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".