Is the interaction of CNP with tubulin and microtubules required for process extension in oligodendrocytes?
Bibliographic record
Abstract
Oligodendrocytes (ODC) differentiate and undergo vast membrane synthesis and process extension to form myelin. What are the molecular mechanisms underlying these events? The myelin protein, CNP, appears to play an important role. Recent work from our lab and others provide strong evidence that CNP is associated with the cytoskeleton and may be involved in process extension. Intriguingly, CNP has an enzymatic activity, whose in vivo relevance is unknown, since substrates with 2′,3′‐cyclic termini have not yet been determined for CNP. To elucidate the function of CNP, a 55‐kDa polypeptide, which copurifies with CNP by immunoprecipitation from rat brain, was identified as tubulin by mass spectrometry. Cultured ODC and CNP‐transfected COS‐7 cells showed extensive microtubule colocalization along the main processes and the cell body. COS‐7 cells expressing high levels of CNP exhibited major morphological changes similar to cultured ODC: rounding of the cell body, process extension, and extensive branching of the processes. Deletion mutant studies reveal that tubulin binding and cell transformation are mediated by the C‐terminal catalytic domain. However, the catalytic activity of CNP is not responsible for these morphological changes, since expression of enzymatic inactive mutants in non‐neuronal cells resembled cells expressing wild‐type CNP. Furthermore, RICH (Regeneration Induced CNPase Homologue), a protein that is expressed in fish retinal ganglion cells and shares extensive homology with CNP in the C‐terminal domain, can bind to tubulin and cause similar cytoskeletal transformations in non‐neuronal cells. Our results suggest that binding of CNP to microtubules facilitates cytoskeletal rearrangements necessary for process extension and myelination in ODC. Acknowledgements: Supported by the CIHR and FCAR.
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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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".