Role of N‐glycosylation in the stability of Ca <sub>V</sub> α2δ1
Bibliographic record
Abstract
L‐type Ca V 1.2 channels play a key role in the excitation‐contraction coupling in the heart. They are formed of a pore‐forming Ca V α1 subunit in complex with the intracellular Ca V β and the disulfur‐linked Ca V α2δ accessory subunits. Ca V α2δ significantly increases peak current densities of Ca V 1.2. The mechanism underlying this effect is still under study but requires that Ca V α2δ be trafficked at the cell surface. Ca V α2δ contains 18 putative N‐glycosylation sites. A study was carried out to i dentify the role of N‐glycosylation in the trafficking and protein stability of the subunit Ca V α2δ. Site‐directed mutagenesis was used to modify the asparagine residues (individually or in combination) to the conservative glutamine residue. Surface density and protein stability were evaluated using a flow cytometry assay using a constitutively fluorescent Ca V α2δ construct. Preliminary data show that the cell surface and total protein densities of Ca V α2δ decreased proportionally to the number of mutations. Functional analysis of the same constructs using whole‐cell patch clamp recordings in HEK cells, confirmed that the peak current density of Ca V 1.2 decreased in the presence of the Ca V α2δ mutants. These results confirm that the surface expression of Ca V α2δ plays a critical role in the function of L‐type Ca V 1.2 channels. Work is under way to identify the most critical residues in this process. Ultimately, our studies will shed light on the molecular mechanism accounting for the modulation of L‐type Ca 2+ currents by the auxiliary Ca V α2δ subunit.
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) | 0.000 | 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 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".