Furin interacts with proMT1-MMP and integrin αV at specialized domains of renal cell plasma membrane
Why this work is in the frame
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Bibliographic record
Abstract
Matrix metalloproteinases (MMPs) and integrins are essential for cell and extracellular matrix homeostasis. Both membrane type-1 MMP (MT1-MMP) and the integrin alphaV subunit are fully activated upon cleavage at a furin recognition site. Furin is shuttled to the cell surface through the trans-Golgi network and endosomal system, and its only known role on plasma membrane consists in activation of opportunistic pathogenic entities. Here, we report findings about the interaction of furin with MT1-MMP and the integrin alphaV at the cell surface. By using in vivo gene delivery, western blotting and immunogold electron microscopy, we provide evidence of significant pools of furin and proMT1-MMP along the surface of cells lining basement membranes. Moreover, furin and integrin alphaV are frequently found associated with the slit diaphragm of renal podocytes and around endothelial fenestrations. ProMT1-MMP, by contrast, is concentrated at the slit diaphragm. Coimmunoprecipitations and double immunogold labelings indicate that furin interacts with proMT1-MMP and alphaV at points of insertion of the slit diaphragm. Our results suggest that these focalized complexes could trigger basement membrane proteolysis either directly by activation of proMT1-MMP or indirectly by promoting activation of proMMP2.
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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 it