LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction
Bibliographic record
Abstract
Parkinson's disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation of mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role in the regulation of synaptic plasticity. Here we demonstrate that postsynaptic knockdown of the fly homologue of LRRK2 thwarts retrograde, homeostatic synaptic compensation at the larval neuromuscular junction. Conversely, postsynaptic overexpression of either the fly or human LRRK2 transgene induces a retrograde enhancement of presynaptic neurotransmitter release by increasing the size of the release ready pool of vesicles. We show that LRRK2 promotes cap-dependent translation and identify Furin 1 as its translational target, which is required for the synaptic function of LRRK2. As the regulation of synaptic homeostasis plays a fundamental role in ensuring normal and stable synaptic function, our findings suggest that aberrant function of LRRK2 may lead to destabilization of neural circuits.
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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 | 0.000 | 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 | 0.001 | 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".