RNF13 variants L311S and L312P associated with developmental epileptic encephalopathy alter dendritic organization in hippocampal neurons
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
gene were reported to cause DEE73. Specifically, two leucines from the ubiquitin E3 ligase RNF13 are converted to serine or proline (L311S and L312P). These mutations are located within a dileucine motif, which impairs RNF13's capacity to interact with AP-3. A second motif allows RNF13 to interact with AP-1 when the dileucine sorting motif is altered. The present study demonstrates that RNF13 variants L311S and L312P are trafficked through an AP-1-dependent pathway in HeLa cells. In cultures of primary rat hippocampal neurons, the protein level of the variants is significantly higher in dendrites than for wild-type protein. L311S and L312P variants alter dendritic components similarly to an RNF13 AP-3-defective binding variant or a dominant negative for RNF13's ubiquitin ligase activity. Compared to non-transfected neurons, the variants change the distribution of EEA1-positive early endosomes throughout the dendrites. While the WT alters the distribution of lysosomes (Lamp1-positive) in dendrites, the variants only decrease their presence in proximal dendrites. Unlike the variants, RNF13 WT increases the abundance of PSD-95 in distal dendrites. Interestingly, only the variants with altered dileucine motifs decrease the total number of postsynaptic inhibitory protein Gephyrin puncta. This study reports that genetic variants L311S and L312P mainly act as a dominant negative protein. This research provides valuable insights into the dendritic defects that occur when DEE73-associated genetic variants of RNF13 are present.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it