PHOSPHORYLATION OF RyR2 SIMULTANEOUSLY EXPANDS THE DYAD AND REARRANGES THE TETRAMERS
Bibliographic record
Abstract
Abstract We have previously demonstrated that type II ryanodine receptors (RyR2) tetramers can be rapidly rearranged in response to a phosphorylation cocktail. The cocktail modified downstream targets indiscriminately making it impossible to determine whether phosphorylation of RyR2 was an essential element of the response. We therefore used the β-agonist isoproterenol and mice with one of the homozygous mutations, S2030A +/+ , S2808A +/+ , S2814A +/+ , or S2814D +/+ , to address this question and to elucidate the role of these clinically relevant mutations. We measured the length of the dyad using transmission electron microscopy (TEM) and directly visualized RyR2 distribution using dual-tilt electron tomography. We found that: 1) The S2814D mutation, by itself, significantly expanded the dyad and reorganized the tetramers suggesting a direct link between the phosphorylation state of the tetramer and the microarchitecture. 2) All of the wild-type, as well as the S2808A and S2814A mice, had significant expansions of their dyads in response to ISO, while S2030A did not. 3) In agreement with functional data from the same mutants, S2030 and S2808 were necessary for a complete β-adrenergic response, whereas S2814 was not. 4) All the mutated residues had unique effects on the organization of their tetramer arrays. 5) The correlation of structure with function suggests that tetramer-tetramer contacts play an important functional role. We conclude that both the size of the dyad and the arrangement of the tetramers are linked to the state of the channel tetramer and can be dynamically altered by a β-adrenergic receptor agonist. Summary Analysis of RyR2 mutants suggests a direct link between the phosphorylation state of the channel tetramer and the microarchitecture of the dyad. All phosphorylation site mutations produced significant and unique effects on the structure of the dyad and its response to isoproterenol.
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) | 0.002 | 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".