The regulatory and enzymatic functions of CRMPs in neuritogenesis, synaptic plasticity, and gene transcription
Bibliographic record
Abstract
Collapsin response mediator proteins (CRMPs) are ubiquitously expressed in neurons from worms to humans. A cardinal feature of CRMPs is to mediate growth cone collapse in response to Semaphorin-3A signaling through interactions with cytoskeletal proteins. These are critical regulatory roles that CRMPs play during neuritogenesis and neural network formation. Through post-translational modifications, such as phosphorylation, O-GlcNAcylation, SUMOylation, and proteolytic cleavage, CRMPs participate in synaptic plasticity by modulating NMDA receptors, L- and N-type voltage-gated calcium channels (VGCCs), thus affecting neurotransmitter release. CRMPs also possess histone deacetylase (HDAC) activity, which deacetylates histone H4 during neuronal death. Calcium-dependent proteolytic cleavage of CRMPs results in the truncation of CRMPs, producing a large 54 kD fragment (p54). Translocation of the p54 fragment into the nucleus leads to deacetylation of nuclear histone H4 and de-repression of transcription factor E2F1 expression. Increased expression of E2F1 elevates the expression of genes in cell cycle and death. These new and exciting studies lead to the realization that CRMPs are multifunctional proteins with both regulatory and enzymatic functions. Increasing numbers of studies associate these functions of CRMPs with the development of mental and neurological disorders, such as schizophrenia, Alzheimer's diseases, brain trauma, and stroke. This review focuses on new evidence showing the regulatory and enzymatic functions of CRMPs and highlights recent understandings of CRMPs' roles in neurological diseases.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".