Defining the mechanisms by which palmitoylation regulates the localization and function of RGS4
Bibliographic record
Abstract
Regulators of G‐Protein Signalling (RGS) proteins are strong candidates for modulating cardiovascular signalling based on their high expression in cardiac and sinoatrial node myocytes, and their ability to potently inhibit heterotrimeric G‐proteins. RGS4 regulates G‐protein function at the plasma membrane (PM) and it has been demonstrated that palmitoylation, the post‐translational addition of a 16 carbon palmitate group to cysteine, is important for RGS4 translocation to the PM. Confocal microscopy data demonstrated that mutation of cysteine residues 2 and 12 removed RGS4 localization to the PM. Calcium imaging confirmed that RGS4‐C2A,C12A elicited less inhibition of Gq‐dependent calcium release than wildtype in HEK293T cells. A library of 23 mammalian palmitoyl‐acyl transferase enzymes has been cloned and isolated, each sharing a conserved catalytic Asp‐His‐His‐Cys (DHHC) site [Fukata et al, 2006]. We set out to establish the DHHC isoforms that regulate the localization and function of RGS4 in HEK cells. We created dominant negative mutations of five DHHCs most highly expressed in HEK cells. Confocal microscopy data showed that co‐transfection of mutant DHHCs 3 and 7 with RGS4 removed localization of RGS4 to the PM. Further studies will examine changes in Gq‐dependent calcium release following transfection of RGS4 in HEK cells where target DHHCs are knocked down using siRNAs. This study was funded by the Heart and Stroke Foundation of Ontario Grant‐in‐Aid Program grants T6799 and the Heart and Stroke/Richard Lewar Centre of Excellence Studentship Award.
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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 | 0.001 |
| 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".