Regulation of Kv2.1 biogenesis and gating by candidate disease-linked Kv6.1 variants
Bibliographic record
Abstract
Silent voltage-gated potassium channel subunits are enigmatic ion channels in the Kv5, Kv6, Kv8, and Kv9 families, which do not generate functional homomers, but instead assemble and modify the function of Kv2 family channels. While these biophysical consequences have been recognized, knowledge on physiological roles and pathologies associated with silent voltage-gated potassium channel subunits is not well developed. In this study, we investigated the functional effects of two Kv6.1 variants identified in either a pediatric patient (Kv6.1[L284P]), or a calf (Kv6.1[W416C]), which exhibited anatomical abnormalities. Kv2.1 current was reduced significantly when coexpressed with either Kv6.1 or Kv6.1[L284P], and even more dramatically with Kv6.1[W416C], which led to nearly complete suppression of Kv2.1 current. These mutants also attenuated Kv6.1-mediated effects on inactivation of Kv2.1. Interestingly, protein expression levels of Kv6.1 variants are not significantly affected when subunits are expressed alone. However, coexpression with Kv2.1 decreases expression of both Kv2.1 and Kv6.1 (and variants), and this effect is particularly powerful for Kv6.1[W416C]. Additionally, we report that Kv2.1 promotes phosphorylation of Kv6.1, but this is largely absent in the Kv6.1[W416C] mutant. Overall, effects of Kv6.1[W416C] are prominent, while Kv6.1[L284P]-mediated effects are much weaker and often difficult to distinguish from WT Kv6.1, and a direct causal link to anatomical abnormalities will require further investigation. Our findings highlight that Kv6.1 and variants influence expression and gating properties of Kv2.1, and also that coassembly with Kv2.1 leads to previously unrecognized posttranslational modifications of Kv6.1.
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.
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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".