Cullin-RING E3 ubiquitin ligase 4 controls axonal morphogenesis during neuronal development
Bibliographic record
Abstract
Abstract Neuritogenesis is critical for the establishment of proper neuronal connections during brain development. Thus, its failure causes neurodevelopmental defects such as intellectual disabilities. Cullin-RING E3 ubiquitin-ligase complexes are involved in neurodevelopmental processes including neurite outgrowth, migration, and differentiation via regulation of protein stability. In this study, we demonstrate a novel regulatory function of Cullin-RING E3 ubiquitin-ligase 4 (CRL4) in neurite morphogenesis during early neurodevelopment. Cul4a and Cul4b, core scaffold proteins of CRL4, are highly expressed and activated in the cytosolic compartment of developing neuron, and they are regulated by neuronal stimulation via N-methyl D-aspartate (NMDA) receptor signaling. CRL4 also interacts with cytoskeleton-regulating proteins involved in neurite morphogenesis in neurons. Notably, CRL4 inhibition enhances axonal extension and branching in developing neurons. Conversely, Cul4a overexpression suppresses basal and NMDA-enhanced axonal outgrowth. Furthermore, CRL4 regulates the stability of Doublecortin protein recruited by Cereblon. Taken together, we suggest a novel role of CRL4 in proper axonal morphogenesis in developing neurons by regulating cytoskeleton-regulating proteins.
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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".