Regulation of the Human Ether‐a‐go‐go Related Gene (hERG) Potassium Channel by Nedd4 Family Interacting Proteins (Ndfips)
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
The cardiac electrical disorder long QT syndrome (LQTS) predisposes affected individuals to high risks of ventricular arrhythmias and sudden death. Dysfunction of the human ether‐a‐go‐go related gene (hERG)‐encoded rapidly activating delayed rectifier K + channel (I Kr ) is a major cause of LQTS. The expression of hERG channels is controlled by the anterograde trafficking of newly synthesized channels to and the retrograde degradation of existing channels from the plasma membrane. We have previously shown that the E3 ubiquitin ligase Nedd4‐2 (neuronal precursor cell expressed, developmentally down‐regulated protein 4 type 2) targets the PY motif of hERG channels to initiate channel degradation. Although both premature and mature hERG channels contain the PY motif, Nedd4‐2 selectively mediates the degradation of mature hERG channels. Here, using whole‐cell patch clamp, Western blot and immunocytochemical analyses, we demonstrate that Nedd4‐2 is directed to specific cellular compartments by the Nedd4 family interacting proteins, Ndfip1 and Ndfip2. Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4‐2 to target mature hERG proteins for degradation during channel trafficking to the plasma membrane. Although Ndfip2 also recruits Nedd4‐2 to the Golgi apparatus to some extent, it mainly recruits Nedd4‐2 to the multivesicular bodies (MVBs), which impedes the degradation of internalized hERG proteins. These findings extend our understanding of hERG channel regulation and provide information which may be useful for the rescue of impaired hERG function in LQTS. (Supported by the Natural Sciences and Engineering Research Council of Canada and the Heart and Stroke Foundation of Ontario)
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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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