Retrieval trafficking plays an important role in homeostasis of hERG expression at the plasma membrane (604.2)
Bibliographic record
Abstract
The human ether‐a‐go‐go‐related gene (hERG) encodes the α‐subunit of the rapidly activating delayed rectifier potassium channel (I Kr ). A reduction in hERG expression on the plasma membrane causes long QT syndrome, predisposing affected individuals to high risk of cardiac arrhythmias and sudden death. We previously reported that plasmalemmal hERG channels are vigorously internalized under certain conditions such as hypokalemia. Whether internalized channels can recycle back to the membrane remains unknown. In this study, using Western blot and patch clamp techniques, we observed that an enhanced recovery rate of I Kr is associated with an increased endocytosis of hERG channels after exposure of cells to hypokalemic conditions. This observation is not due to increased synthesis since hERG mRNA expression was not increased by hypokalemic treatment and the enhanced recovery was not affected by the inhibition of protein synthesis using cycloheximide. Using fluorescent labeling, we directly monitored the retrieval trafficking of internalized hERG channels to the plasma membrane. Co‐immunoprecipitation experiments reveal that hERG channels are associated with the GTPase Rab11, but not Rab4. Interference with Rab11 function but not Rab4 led to decreased hERG expression and function. Our data provide novel insights into the recycling mechanisms that regulate the homeostasis of membrane‐bound hERG channels. Supported by the Canadian Institutes of Health Research ‐ CIHR
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".