Involvement of CaMK‐IIδ and gelsolin in Cd<sup>2+</sup>‐dependent cytoskeletal effects in mesangial cells
Bibliographic record
Abstract
Cadmium is a toxic metal with pleiotropic effects on cell death and survival. The mesangial cell is particularly responsive to Cd's effects on kinase signaling pathways and cytoskeletal dynamics. Here we show that CaMK-II is a participant in the cytoskeletal effects of Cd(2+) . A major mesangial cell isoform, CaMK-IIδ, was identified in pellets of DNase I pull-downs and cytosolic immunoprecipitates of G-actin. CaMK-IIδ was also present in Triton X-100-insoluble cytoskeletal preparations and translocated to the cytoskeleton in a concentration-dependent manner in Cd-treated cells. Translocation was suppressed by KN93, an inhibitor of CaMK-II phosphorylation. In vitro actin polymerization studies indicated that recombinant CaMK-IIδ sequestered actin monomer. Cytoskeletal preparations from Cd-treated cells decrease the rate of polymerization, but KN93 co-treatment prevents this effect. Over-expressed CaMK-IIδ also translocated to the cytoskeleton upon Cd exposure, and this was prevented by KN93. Conversely, siRNA silencing of CaMK-IIδ increases the effect of cytoskeletal extracts on actin polymerization, and abrogates the effect of Cd. The actin capping and severing protein, gelsolin, translocates to the cytoskeleton in the presence of Cd(2+) , dependent upon the phosphorylation of CaMK-II, and is recovered together with actin and CaMK-IIδ in G-actin pull-downs and F-actin sedimentation. Translocation is accompanied by generation of a 50 kDa gelsolin fragment whose appearance is prevented by KN93 and CaMK-IIδ silencing. We conclude that cytoskeletal effects of Cd in mesangial cells are partially mediated by Cd-dependent activation of CaMK-IIδ, binding of CaMK-IIδ and gelsolin to actin filaments, and cleavage of gelsolin.
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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 | 0.001 | 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".