Sensing nerve injury at the axonal ER: Activated Luman/CREB3 serves as a novel axonally synthesized retrograde regeneration signal
Bibliographic record
Abstract
Luman/cAMP response element binding protein 3 is an endoplasmic reticulum (ER) transmembrane basic leucine zipper transcription factor whose mRNA and protein localize to adult sensory axons, the latter with axonal ER components along the axon length. Here we show that axon-derived Luman plays an important role in relaying information about axonal injury to the neuronal cell body. Axotomy induces axonal Luman synthesis and also release from the axonal ER of Luman's transcriptionally active amino terminus, which is transported to the cell body in an importin-mediated manner. Visualization of the activation and retrograde translocation of Luman into the nucleus in real time both in vivo and in vitro was accomplished using a specially created N- and C-terminal-tagged Luman adenoviral vector. Small interfering RNA used to reduce Luman expression either neuronally or just axonally significantly impaired the ability of 24-h injury-conditioned sensory neurons to extend the regeneration-associated elongating form of axon growth but had no impact on axon outgrowth in naïve neurons. Collectively, these findings link injury-associated axonal ER responses proximal to the site of injury to the intrinsic regenerative growth capacity of adult sensory neurons.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".