The Leucine-Rich Repeat Region of CARMIL1 Regulates IL-1-Mediated ERK Activation, MMP Expression, and Collagen Degradation
Bibliographic record
Abstract
CARMILs are large, multidomain, membrane-associated proteins that regulate actin assembly and Rho-family GTPases, but their role in inflammatory signaling is not defined. Tandem mass tag mass spectrometry indicated that, in fibroblasts, CARMIL1 associates with interleukin (IL)-1 signaling molecules. Immunoprecipitation of cells transfected with CARMIL1 mutants showed that the leucine-rich repeat (LRR) region of CARMIL1 associates with IL-1 receptor type 1 (IL-1R1) and IL-1 receptor-associated kinase (IRAK). Knockout of CARMIL1 by CRISPR-Cas9 reduced IL-1-induced ERK activation by 72% and MMP3 expression by 40%. Compared with CARMIL1 wild-type (WT), cells expressing mutant CARMIL1 lacking its LRR domain exhibited 45% lower ERK activation and 40% lower MMP3 expression. In fibroblasts transduced with a cell-permeable, TAT CARMIL1 peptide that competed with IL-1R1 and IRAK binding to the LRR of CARMIL1, collagen degradation was reduced by 43%. As the LRR of CARMIL1 evidently regulates IL-1 signaling, CARMIL1 could become a target for anti-inflammatory drug development.
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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".