MRIP Regulates the Myosin IIA Activity and DDR1 Function to Enable Collagen Tractional Remodeling
Bibliographic record
Abstract
DDR1 is a collagen adhesion-mechanoreceptor expressed in fibrotic lesions. DDR1 mediates non-muscle myosin IIA (NMIIA)-dependent collagen remodeling. We discovered that the myosin phosphatase Rho-interacting protein (MRIP), is enriched in DDR1-NMIIA adhesions on collagen. MRIP regulates RhoA- and myosin phosphatase-dependent myosin activity. We hypothesized that MRIP regulates DDR1-NMIIA interactions to enable cell migration and collagen tractional remodeling. After deletion of MRIP in β1-integrin null cells expressing DDR1, in vitro wound closure, collagen realignment, and contraction were reduced. Cells expressing DDR1 and MRIP formed larger and more abundant DDR1 clusters on collagen than cells cultured on fibronectin or cells expressing DDR1 but null for MRIP or cells expressing a non-activating DDR1 mutant. Deletion of MRIP reduced DDR1 autophosphorylation and blocked myosin light chain-dependent contraction. Deletion of MRIP did not disrupt the association of DDR1 with NMIIA. We conclude that MRIP regulates NMIIA-dependent DDR1 cluster growth and activation. Accordingly, MRIP may provide a novel drug target for dysfunctional DDR1-related collagen tractional remodeling in fibrosis.
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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".