C-terminal Domain of Chromogranin B Regulates Intracellular Calcium Signaling
Bibliographic record
Abstract
The versatility of intracellular calcium as a second messenger is seen in its ability to mediate opposing events such as neuronal cell growth and apoptosis. A leading hypothesis used to explain how calcium regulates such divergent signaling pathways is that molecules responsible for maintaining calcium homeostasis have multiple roles. For example, chromogranin B (CGB), a calcium binding protein found in secretory granules and in the lumen of the endoplasmic reticulum, buffers calcium and also binds to and amplifies the activity of the inositol 1,4,5-trisphosphate receptor (InsP(3)R). Previous studies have identified two conserved domains of CGB, an N-terminal domain (N-CGB) and a C-terminal domain (C-CGB). N-CGB binds to the third intraluminal loop of the InsP(3)R and inhibits binding of full-length CGB. This displacement of CGB decreases InsP(3)R-dependent calcium release and alters normal signaling patterns. In the present study, we further characterized the role of N-CGB and identified roles for C-CGB. The effect of N-CGB on calcium release depended upon endogenous levels of cellular CGB, whereas the regulatory effect of C-CGB was apparent regardless of endogenous levels of CGB. When either full-length CGB or C-CGB was expressed in cells, calcium transients were increased. Additionally, the calcium signal initiation site was altered upon C-CGB expression in neuronally differentiated PC12 and SHSY5Y cells. These results show that CGB has numerous regulatory roles and that CGB is a critical component in modulating InsP(3)R-dependent calcium signaling.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".