A new role for Dysferlin in endothelial cell adhesion and neo‐vascularization
Bibliographic record
Abstract
Dysferlin is a member of the Ferlin family of proteins known to regulate plasma membrane integrity and are linked to muscular dystrophy. However, the peripheral roles of Dysferlin in non‐muscle cells remain virtually unknown. By performing proteomic analysis of caveolae/lipid rafts, we reported that endothelial cells (EC) express Myoferlin and that it mediates plasma membrane translocation of vascular endothelial growth factor receptor‐2 (VEGFR‐2). Herein, we show by Northern and Western blot as well as by immunohistochemistry that EC and intact blood vessels of rodent and human origin all express Dysferlin but that its presence is not required for VEGFR‐2 signaling. Instead, loss of Dysferlin in EC results in deficient adhesion, detachment and growth arrest in sub‐confluent cells whereas confluent EC monolayers are remarkably resistant to cell detachment. In Dysferlin‐null mice, delivery of VEGF, an EC‐specific angiogenic agonist, results in blunted neo‐angiogenesis compared to WT mice. Mechanistically, loss of Dysferlin causes poly‐ubiquitination and proteasomal degradation of platelet endothelial cellular adhesion molecule‐1 (PECAM‐1/CD31). Our discovery that Dysferlin is a regulator of EC adhesion and neo‐vascularization broadens the functional scope of this family of proteins and suggest that specialization exist between the different Ferlins and their respective membrane‐based cargo.
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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".