Semaphorin 5B mediates synapse elimination in hippocampal neurons
Bibliographic record
Abstract
BACKGROUND: Semaphorins are known to play an important role in axon guidance and growth by triggering dynamic rearrangements of the actin cytoskeleton in the neuronal growth cone. Intriguingly, some of these guidance molecules are persistently expressed after axonal pathfinding and target recognition are completed. Although their function at these later stages is poorly understood, recent findings suggest a role for these proteins in regulating synaptic connections. RESULTS: Here we demonstrate that semaphorin 5B (Sema5B) regulates the elimination of synaptic connections in cultured hippocampal neurons. We show that Sema5B is proteolytically processed in neonatal brains and primary hippocampal cultures, resulting in the secretion of Sema5B fragments that include the biologically active semaphorin domain. Overexpression of full-length Sema5B in hippocampal neurons reduces synapse number while expression of a Sema5B construct lacking the semaphorin domain has no effect. Moreover, bath application with the proteolytically processed, secreted fragments containing the semaphorin domain of Sema5B, results in a rapid elimination of synaptic connections as demonstrated by time-lapse imaging. Conversely, depletion of endogenous Sema5B using RNA interference results in a significant increase in synapse number as well as a significant increase in the size of presynaptic and postsynaptic compartments. CONCLUSION: Our results demonstrate that in addition to its role as a guidance cue, Sema5B regulates the development and maintenance of synapse size and number in hippocampal neurons. In addition, proteolytic cleavage of Sema5B results in the release of a potentially diffusible semaphorin domain that is a necessary component for its biological function in the regulation of synapse morphology.
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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) | 0.001 | 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".