Role of the SNARE protein SNAP23 on cAMP-stimulated renin release in mouse juxtaglomerular cells
Bibliographic record
Abstract
Renin, the rate-limiting enzyme in the formation of angiotensin II, is synthesized and stored in granules in juxtaglomerular (JG) cells. Therefore, the controlled mechanism involved in renin release is essential for the regulation of blood pressure. Exocytosis of renin-containing granules is likely involved in renin release; a process stimulated by cAMP. We found that the "soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor" (SNARE) protein VAMP2 mediates cAMP-stimulated renin release and exocytosis in JG cells. To mediate exocytosis, VAMP2 must interact with a synaptosome-associated protein (SNAP). In the renal cortex, the isoform SNAP23 is abundantly expressed. We hypothesized that SNAP23 mediates cAMP-stimulated renin release from primary cultures of mouse JG cells. We found that SNAP23 protein is expressed and colocalized with renin-containing granules in primary cultures of mouse JG cell lysates. Thus, we then tested the involvement of SNAP23 in cAMP-stimulated renin release by transducing JG cells with a dominant-negative SNAP23 construct. In control JG cells transduced with a scrambled sequence, increasing cAMP stimulated renin release from 1.3 ± 0.3 to 5.3 ± 1.2% of renin content. In cells transduced with dominant-negative SNAP23, cAMP increased renin from 1.0 ± 0.1 to 3.0 ± 0.6% of renin content, a 50% blockade. Botulinum toxin E, which cleaves and inactivates SNAP23, reduced cAMP-stimulated renin release by 42 ± 17%. Finally, adenovirus-mediated silencing of SNAP23 significantly blocked cAMP-stimulated renin release by 50 ± 13%. We concluded that the SNARE protein SNAP23 mediates cAMP-stimulated renin release. These data show that renin release is a SNARE-dependent process.
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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 | 0.001 |
| 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 | 0.000 |
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".