Isoform-dependent Formation of Heteromeric Ca2+ Release Channels (Ryanodine Receptors)
Bibliographic record
Abstract
Three ryanodine receptor (RyR) isoforms, RyR1, RyR2, and RyR3, are expressed in mammalian tissues. It is unclear whether RyR isoforms are capable of forming heteromeric channels. To investigate their ability to form heteromeric channels, we co-expressed different RyR isoforms in HEK293 cells and examined their interactions biochemically and functionally. Immunoprecipitation studies revealed that RyR2 is able to interact physically with RyR3 and RyR1 in HEK293 cells and that RyR1 does not interact with RyR3. Co-expression of a ryanodine binding deficient mutant of RyR2, RyR2 (I4827T), with RyR3 (wt) restored [(3)H]ryanodine binding to the mutant. Interactions between RyR isoforms were further assessed by complementation analysis using mutants RyR2 (I4827T), RyR2 (E3987A), RyR3 (I4732T), RyR3 (E3885A), and RyR1 (E4032A), all of which are deficient in caffeine response. Caffeine-induced Ca(2+) release was restored in HEK293 cells co-transfected with mutants RyR2 (I4827T) and RyR3 (E3885A), RyR2 (E3987A) and RyR3 (I4732T), or RyR2 (I4827T) and RyR1 (E4032A), but not with RyR1 (E4032A) and RyR3 (I4732T), indicating that mutants of RyR2 and RyR3, or RyR2 and RyR1, but not RyR1 and RyR3, are able to complement each other. Co-expression of RyR3 (wt) and a pore mutant of RyR2, RyR2 (G4824A), produced regulatable single channels with intermediate unitary conductances. These observations demonstrate that RyR2 is capable of forming functional heteromeric channels with RyR3 and RyR1, whereas RyR1 is incapable of forming heteromeric channels with RyR3.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".