Bcl-2 proteins, cell migration and embryonic development: lessons from zebrafish
Bibliographic record
Abstract
B-cell lymphoma-2 (Bcl-2) was cloned 30 years ago and associated with B-cell follicular lymphoma. A number of Bcl-2 homologs were identified later on. Importantly, the Bcl-2 family was found to control the mitochondrial outer membrane permeabilization: a key step of the mitochondrial pathway of apoptosis.1 Bcl-2 homologs are evolutionarily conserved throughout metazoans and considered as the hallmarks of multicellularity. Genetic manipulation in nematodes and mice demonstrated that the bcl-2 family has a pivotal role in tissue homeostasis by controlling cell death; however, an increased number of in vitro studies have identified additional non-apoptotic functions, suggesting that Bcl-2 proteins are in fact multitask factors (Figure 1a).2 Figure 1 Non-apoptotic functions of the Bcl-2 family of proteins. (a) Simplified representation of Bcl-2 proteins functions. Bcl-2 proteins are multitask factors and linked to non-apoptotic functions. The top panel represents the different Ca2+-independent ... Besides their mitochondrial localization, Bcl-2 proteins are also found in the endoplasmic reticulum (ER). In fact, a number of them contribute to apoptosis regulation though the control of Ca2+ exchanges at the level of the ER/mitochondria interface. Indeed physical proximity between these organelles creates intracellular microdomains, considered as Ca2+ hotspots.3 Mitochondria constantly uptake Ca2+ to ensure their physiological functions; they are also able to rapidly uptake Ca2+ when massively released from the ER, acting as a genuine Ca2+ buffer. This fast accumulation may lead to mitochondrial Ca2+ overload and, depending on Ca2+ levels, the cells will undergo apoptosis or necrosis.4 Bcl-2 proteins control Ca2+ exchanges through direct interactions with ER Ca2+ channels and pumps including the Inositol 1,4,5-Trisphosphate receptor (IP3R), the Ca2+-ATPase (SERCA) pump, the ryanodine receptor, the Bax inhibitor-1 channel, as well as, the voltage-dependent anion channel (VDAC) at the mitochondria (reviewed in Bonneau et al.2). It was reported that overexpression of Bcl-2 may lead to a decrease of the ER Ca2+ load,5 and the ability of Bcl-2 proteins to regulate intracellular Ca2+ homeostasis was linked to non-apoptotic functions (Figure 1a).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".