STIM1-mediated bidirectional regulation of Ca2+ entry through voltage-gated calcium channels (VGCC) and calcium-release activated channels (CRAC)
Bibliographic record
Abstract
The spatial and temporal regulation of cellular calcium signals is modulated via two main Ca(2+) entry routes. Voltage-gated Ca(2+) channels (VGCC) and Ca(2+)-release activated channels (CRAC) enable Ca(2+) flow into electrically excitable and non-excitable cells, respectively. VGCC are well characterized transducers of electrical activity that allow Ca(2+) signaling into the cell in response to action potentials or subthreshold depolarizing stimuli. The identification of STromal Interaction Molecule (STIM) and Orai proteins has provided significant insights into the understanding of CRAC function and regulation. This review will summarize the current state of knowledge of STIM-Orai interaction and their contribution to cellular Ca(2+) handling mechanisms. We will then discuss the bidirectional actions of STIM1 on VGCC and CRAC. In contrast to the stimulatory role of STIM1 on Orai channel activity that facilitates Ca(2+) entry, recent reports indicated the ability of STIM1 to suppress VGCC activity. This new concept changes our traditional understanding of Ca(2+) handling mechanisms and highlights the existence of dynamically regulated signaling complexes of surface expressed ion channels and intracellular store membrane-embedded Ca(2+) sensors. Overall, STIM1 is emerging as a new class of regulatory proteins that fine-tunes Ca(2+) entry in response to endoplasmic/sarcoplasmic reticulum stress.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| 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".