The EphA4 Receptor Regulates Neuronal Morphology through SPAR-Mediated Inactivation of Rap GTPases
Bibliographic record
Abstract
Eph receptors play critical roles in the establishment and remodeling of neuronal connections, but the signaling pathways involved are not fully understood. We have identified a novel interaction between the C terminus of the EphA4 receptor and the PDZ domain of the GTPase-activating protein spine-associated RapGAP (SPAR). In neuronal cells, this binding mediates EphA4-dependent inactivation of the closely related GTPases Rap1 and Rap2, which have recently been implicated in the regulation of dendritic spine morphology and synaptic plasticity. We show that SPAR-mediated inactivation of Rap1, but not Rap2, is critical for ephrin-A-dependent growth cone collapse in hippocampal neurons and decreased integrin-mediated adhesion in neuronal cells. Distinctive effects of constitutively active Rap1 and Rap2 on the morphology of growth cones and dendritic spines support the idea that these two GTPases have different functions in neurons. Together, our data implicate SPAR as an important signaling intermediate that links the EphA4 receptor with Rap GTPase function in the regulation of neuronal morphology.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".